1. Introduction
It has been more than 2 years since coronavirus disease 2019 (COVID-19) wreaked havoc worldwide. The virus has shown strong mutational ability in the early stages of the epidemic. To date, there are five “variants of concern” (VOC) proposed by the World Health Organization (WHO), namely, Alpha, Beta, Gamma, Delta, and Omicron.
The Delta variant first appeared in India in October 2020. By September 2021, patients with Delta variants had appeared in 185 countries worldwide. The Delta variant was believed to spread faster than the other variants at the time.[1] On November 26, 2021, the WHO designated variant B.1.1.529, a VOC named Omicron.[2] As of April 2022, the relative proportion of BA.2 among Omicron descendant lineages has risen to 93.6%, while BA.1.1 accounts for 4.8%, and BA.1 and BA.3 account for less than 0.1% of all Omicron lineages. At that time, BA.2 has taken the lead in 68 countries with available sequence data and all six WHO regions.[3] According to the PANGO lineage, Omicron now includes BA.1, BA.2, BA.3, BA.4, and BA.5. During the COVID-19 pandemic, the Omicron variant of SARS-CoV-2 has had the highest number of mutations. According to previous studies, the Omicron variant is more infectious and capable of evading the immune system than the early wild-type strains and other variants.
The Omicron variant of SARS-CoV-2 shows less severe clinical characteristics and higher transmissibility. However, a detailed understanding of the reduction in clinical presentation compared with the Delta variant is required. This retrospective comparative cohort study included 109 patients infected with the Delta variant of SARS-CoV-2 and 183 patients infected with the Omicron variant from January 19, 2022, to April 1, 2022, the emergency ward of Beijing Ditan Hospital. Clinical data, genome analysis, laboratory parameters, viral shedding time, and computed tomography (CT) images were collected to compare and analyze the clinical and genomic characteristics of the two groups.
2. Materials and methods
2.1. Ethical approval
The study was approved by the institutional review board of Beijing Ditan Hospital, Capital Medical University in Beijing (approval number JDLY2020-020-01). This study complies with the Declaration of Helsinki.
2.2. Study design and recruitment of cases
We built a cloud database of COVID-19 patients in Beijing Ditan Hospital in January 2020. In this retrospective study, we extracted a total of 292 COVID-19 cases from January to April 2022, and the cases were divided into Delta variant and Omicron variant groups. According to the 9th edition of the Diagnosis and Treatment Protocol for COVID-19 Patients,[4] COVID-19 patients were diagnosed, and the clinical severity was divided into the following four grades: mild, moderate, severe, and critical. Furthermore, asymptomatic patients who had positive reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results but no clinical symptoms were admitted to the hospital. All patients were discharged at the time of the study.
2.3. Data collection
Information on the two groups for the 292 COVID-19 cases was obtained from the cloud database. We reviewed the patients’ medical records by collecting their basic information, clinical data, laboratory test results, and CT images.
2.4. Laboratory testing
RT-qPCR was performed on oropharyngeal, nasopharyngeal, or sputum specimens using the SARS-CoV-2 nucleic acid test kit (BioGerm, Shanghai, China) with a fluorescence PCR detector, according to the manufacturer’s instructions. The results are expressed as the cycle threshold (Ct) for the ORF1ab and N genes of SARS-CoV-2. In addition, anti-SARS-CoV-2 antibodies were evaluated using a chemiluminescence immunoassay (CLIA; Bioscience, Chongqing, China).
2.5. Next-generation sequencing
For whole-genome sequencing, we sent the patients’ oropharyngeal, nasopharyngeal, or sputum samples to the Beijing Center for Disease Prevention and Control. RNA from the viruses was isolated using automated nucleic acid purification (KingFisher Flex Purification System, Thermo, USA). Using 8 μL of input RNA and random hexamers, first-strand cDNA was synthesized using the SuperScript IV First-Strand Synthesis System (Invitrogen, Waltham, MA, USA). Using the ARTIC nCoV-2019 sequencing technique v4.1 (https://github.com/artic-network/artic-ncov2019), 25–32 PCR cycles were performed to generate tiled-PCR amplicons. Primers for pools 1 and 2 were synthesized by Sangon (Shanghai, China). Next-generation sequencing libraries were prepared using the Nextera XT Library Prep Kit (Illumina, San Diego, CA, USA) and sequenced on MiniSeq with 2 × 150 paired-end sequencing kits (Illumina, San Diego, CA, USA). Negative control samples were processed and sequenced in parallel for each sequencing run as contamination controls.
2.6. SARS-CoV-2 genome analysis
Quality control and adapter trimming were performed using the CLC Genomics Workbench (v10.0; Qiagen, Germany). Clean reads were mapped to the reference SARS-CoV-2 genome (GenBank: MN908947.3). The CLC Genomics Workbench was used to generate variant calling, genome alignment, and sequence illustrations. MAFFT (v7.0) was used to perform whole-genome sequence alignment. A neighbor-joining phylogenetic tree was generated using the Kimura 2-parameter model with 1,000 bootstrap replicates. Genomic lineage designation was performed using the “PANGO lineage-typing method” (https://cov-lineages.org/). Chiplot software (https://www.chiplot.online) was used to generate the final figure.
2.7. Statistical analysis
SPSS version 25.0 was used to perform the statistical analysis (SPSS; IBM Corp, Armonk, NY, USA). Means and standard deviations were used to describe the continuous normal variables. A significant difference test was performed using the Student t test. The Mann-Whitney U test was used to compare nonnormally distributed continuous variables, and medians and interquartile ranges were used as representations. χ2 and Fisher exact tests were used to compare categorical variables expressed as numbers and percentages. A P value less than 0.05 was considered significant for all two-tailed tests.
3. Results
3.1. Next-generation sequencing and analysis
Sequencing was performed for all 292 COVID-19 cases, and 204 sequences were obtained with a genome coverage of more than 99.0%. We divided the groups according to a clear epidemiological history of the 88 patients whose sequences were not obtained. Pangolin analysis showed that 94 strains belonged to VOC/Delta and the other 110 strains belonged to VOC/Omicron [Figure 1]. In particular, 93 of the 94 Delta strains were assigned to the AY.30 lineage, carrying 41 to 42 nucleotide mutations (including substitutions, insertions, and deletions), and one was the B.1.617.2 lineage, with 41 nucleotide mutations. The number of amino acid mutations (including substitutions, insertions, and deletions) within the spike protein ranged from 10 to 11 in all 94 Delta strains [Figure 2A]. Remarkably, an additional amino acid mutation of N501Y, which is typical of the other four VOCs (Alpha, Beta, Gamma, and Omicron), was observed in one strain.
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Figure 1: Neighbor-joining phylogenetic tree based on the whole-genome sequences of SARS-CoV-2. The strains identified in this study are indicated by dots. The PANGO lineages are marked and colored. The tree was rooted using the strain reference SARS-CoV-2 genome (MN908947.3) in accordance with the root of the PANGO tree.
Figure 2: Amino acid mutations within the spike protein. (A) Amino acid mutations within the spike protein in 94 Delta strains. The nonsynonymous mutations and insertions are indicated by light red and deep red, respectively. No deletion is found in the spike protein. (B) Amino acid mutations within the spike protein in 107 Omicron BA.2 strains (BA.2 and BA.2.2). The synonymous mutations, nonsynonymous mutations, and insertions are indicated by green, light red, and deep red, respectively. No deletion is found in the spike protein.
For the 110 Omicron strains, three were assigned to the BA.1.1 lineage, 53 to the BA.2 lineage, and the other 54 to the BA.2.2 lineage. The number of nucleotide mutations in the BA.1.1, BA.2, and BA.2.2 lineages ranged from 67 to 73, 65 to 70, and 68 to 76, respectively. The number of amino acid mutations within the spike protein ranged from 37 to 39 for BA.1.1 strains and 27 to 33 for BA.2 (BA.2 and BA.2.2) [Figure 2B].
3.2. Basic information and clinical severity of COVID-19 cases
There were 109 patients with the Delta variant, including 85 male (78%) and 24 female (22%) patients. The age was 42.9 ± 13.0 years, including two cases 14 years or younger and seven cases 60 years or older. A total of 183 patients were infected with the Omicron variant, including 77 male patients (42%) and 106 female patients (58%). The median age was 26.0 (15.0–40.0) years, including 40 patients 14 years or younger and 12 patients 60 years or older. For patients 14 years or younger, five were asymptomatic and 35 were mild. Patients in the Delta variant group had more male patients than those in the Omicron group, and the patients were older [Table 1].
Table 1 -
Basic information, clinical severity, and vaccination status of patients in two groups
| Variables |
Delta group (n = 109) |
Omicron group (n = 183) |
P
|
| Sex [n (%)] |
|
|
<0.001 |
| Male |
85 (78) |
77 (42) |
|
| Female |
24 (22) |
106 (58) |
|
| Age (y) |
42.9 ± 13.0 |
26.0 (15.0, 40.0) |
<0.001 |
| Clinical severity level [n (%)] |
|
|
|
| Asymptomatic |
12 (11) |
24 (13) |
0.597 |
| Mild |
38 (35) |
147 (80) |
<0.001 |
| Moderate |
59 (54) |
12 (7) |
<0.001 |
| Severe or critical |
0 |
0 |
|
| Underlying diseases or obesity [n (%)] |
|
|
0.011 |
| Asymptomatic |
1 (4) |
2 (9) |
|
| Mild |
8 (32) |
15 (65) |
|
| Moderate |
16 (64) |
6 (26) |
|
| Aged ≥60 y [n (%)] |
|
|
0.028 |
| Asymptomatic |
0 |
0 |
|
| Mild |
0 |
6 (50) |
|
| Moderate |
7 (100) |
6 (50) |
|
| Aged ≤14 y [n (%)] |
|
|
0.819 |
| Asymptomatic |
1 (50) |
5 (12) |
|
| Mild |
0 |
35 (88) |
|
| Moderate |
1 (50) |
0 |
|
| Vaccinated situation [n (%)] |
|
|
0.003 |
| Unvaccinated |
14 (13) |
22 (12) |
<0.001 |
| Asymptomatic |
1 (7) |
1 (5) |
|
| Mild |
0 |
21 (95) |
|
| Moderate |
13 (93) |
0 |
|
| 1 dose |
3 (3) |
22 (12) |
|
| 2 doses |
25 (23) |
63 (34) |
|
| 3 doses |
67 (61) |
76 (42) |
|
*The continuous normal distributed variables were described as means and standard deviations. The nonnormally distributed continuous variables were described as medians and interquartile ranges.
Among the 109 patients infected with the Delta variant, 59 patients (54%) were moderately and significantly higher than those infected with the Omicron variant, with only 12 moderate patients (7%). In comparison, 147 of 183 patients (80%) infected with the Omicron variant were mildly infected, which was higher than those infected with the Delta variant. There was a significant difference between the two groups. None of the patients in either group developed the severe or critical disease.
Compared with the Omicron group, patients with underlying diseases or obesity or 60 years or older in the Delta group had more severe disease, and there was a significant difference between the two groups (P = 0.011 and P = 0.028, respectively). Most patients 14 years or younger in the Omicron group had mild symptoms [Table 1].
The numbers of unvaccinated patients in the Delta and Omicron groups were 14 and 22, respectively. Thirteen of the 14 unvaccinated patients (93%) in the Delta group were moderate and 21 of the 22 unvaccinated patients (95%) in the Omicron group were mild. There was a significant difference between the two groups (P < 0.001); 61% of patients in the Delta variant group received three vaccine doses, which was higher than that in the Omicron variant group (42%) [Table 1].
3.3. Comparison of symptoms and laboratory tests
The symptoms in the two groups were mainly fever, cough, dry or sore throat, nasal congestion, and a runny nose. Among the 183 patients in the Omicron variant group, 104 (57%) had dry or sore throat symptoms, more than in the Delta variant group, and there was a significant difference between the two groups [Table 2].
Table 2 -
Comparison of symptoms and laboratory tests in the two groups
| Variables |
Delta group (n = 109) |
Omicron group (n = 183) |
P
|
| Symptoms [n (%)] |
|
|
|
| Fever |
66 (61) |
97 (53) |
0.209 |
| Cough |
27 (25) |
63 (34) |
0.084 |
| Dry or sore throat |
37 (34) |
104 (57) |
<0.001 |
| Nasal congestion |
23 (21) |
29 (16) |
0.256 |
| Runny nose |
19 (17) |
29 (16) |
0.724 |
| Fatigue |
6 (6) |
12 (7) |
0.718 |
| Muscle soreness |
12 (11) |
23 (13) |
0.692 |
| Headache |
10 (9) |
9 (5) |
0.154 |
| Loss of smell or taste |
6 (6) |
5 (3) |
0.229 |
| Diarrhea |
2 (2) |
(1) |
0.558 |
| Conjunctivitis |
1 (1) |
0 |
0.373 |
| Laboratory tests * |
|
|
|
| White blood count (×109/L) |
6.6 (4.9–7.9) |
6.1 (4.9–7.6) |
0.278 |
| Neutrophil count (×109/L) |
4.4 (3.3–5.8) |
4.0 (3.1–5.3) |
0.025 |
| Lymphocyte count (×109/L) |
1.3 (1.0–1.7) |
1.3 (0.9–1.9) |
0.361 |
| C-reactive protein (mg/L) |
3.6 (1.2–9.0) |
2.2 (0.6–8.4) |
0.248 |
| Serum amyloid A (mg/L) |
12.4 (4.4–32.4) |
13.7 (4.5–72.7) |
0.227 |
| Alanine aminotransferase (U/L) |
20.5 (15.5–34.1) |
16.4 (11.3–24.0) |
<0.001 |
| Aspartate aminotransferase (U/L) |
20.0 (17.2–25.8) |
20.6 (17.2–26.8) |
0.563 |
| Creatine kinase (μmol/L) |
68.3 ± 13.1 |
58.32 ± 17.0 |
<0.001 |
| Prothrombin time (s) |
11.6 (11.1–12.5) |
12.4 (11.6–13.3) |
<0.001 |
| Activated partial thromboplastin time (s) |
31.7 ± 3.2 |
33.6 (30.8–35.7) |
<0.001 |
| Fibrinogen (mg/dL) |
332.6 ± 72.5 |
302.0 (253.0–369.0) |
0.029 |
|
d-Dimer (mg/L) |
0.3 (0.2–0.5) |
0.4 (0.3–0.6) |
<0.001 |
* The continuous normal distributed variables were described as means and standard deviations. The nonnormally distributed continuous variables were described as medians and interquartile ranges.
In the Delta variant group, fever and cough symptoms were significantly more common in moderate patients than in mild patients. However, there were no significant differences in symptoms between moderate and mild patients in the Omicron variant group. Symptoms of taste or smell loss, diarrhea, and conjunctivitis were less than 10% in both groups [Table 3].
Table 3 -
Comparison of symptoms in patients with moderate and mild severity
| Variables |
Delta group |
Omicron group |
| Moderate (n = 59) |
Mild (n = 38) |
P
|
Moderate (n = 12) |
Mild (n = 147) |
P
|
| Fever [n (%)] |
47 (80) |
19 (50) |
0.002 |
9 (75) |
88 (60) |
0.468 |
| Cough [n (%)] |
21 (36) |
6 (16) |
0.034 |
8 (67) |
55 (37) |
0.092 |
| Dry or sore throat [n (%)] |
18 (31) |
19 (50) |
0.054 |
9 (75) |
95 (65) |
0.681 |
| Nasal congestion, n (%) |
15 (25) |
8 (21) |
0.621 |
1 (8) |
28 (19) |
0.592 |
| Runny nose [n (%)] |
12 (20) |
7 (18) |
0.816 |
0 |
29 (20) |
0.189 |
| Fatigue [n (%)] |
5 (8) |
1 (3) |
0.399 |
0 |
12 (8) |
0.645 |
| Muscle soreness [n (%)] |
7 (12) |
5 (13) |
1.000 |
1 (8) |
22 (15) |
0.840 |
| Headache [n (%)] |
8 (14) |
2 (5) |
0.332 |
1 (8) |
8 (5) |
>0.999 |
| Loss of smell or taste [n (%)] |
3 (5) |
3 (8) |
0.676 |
0 |
5 (3) |
>0.999 |
| Diarrhea [n (%)] |
2 (3) |
0 |
0.518 |
0 |
1 (1) |
>0.999 |
| Conjunctivitis [n (%)] |
1 (2) |
0 |
1.000 |
0 |
0 |
— |
| C-reactive protein (mg/L) * |
4.4 (1.7–10.9) |
3.5 (1.7–9.9) |
0.624 |
6.7 ± 5.2 |
2.5 (0.6–9.8) |
0.257 |
| Serum amyloid A [mg/L, M (Q1 -Q3)] |
17.3 (6.2–37.1) |
11.5 (4.4–43.3) |
0.629 |
12.2 (4.1–58.0) |
22.6 (4.9–103.1) |
0.420 |
| Prothrombin time (s) * |
11.6 (11.1, 12.5) |
11.8 ± 1.1 |
0.896 |
11.9 ± 1.1 |
12.4 (11.7–13.3) |
0.102 |
| Activated partial thromboplastin time (s) * |
31.8 ± 3.6 |
31.8 ± 2.6 |
0.959 |
32.3 ± 2.8 |
33.5 (30.8–35.5) |
0.322 |
| Fibrinogen (mg/dL) * |
346.4 ± 75.9 |
319.3 ± 67.7 |
0.085 |
345.9 ± 67.8 |
313.0 (253.0–374.0) |
0.187 |
|
d-dimer [mg/L, M (Q1–Q3)] |
0.3 (0.3–0.5) |
0.3 (0.2–0.5) |
0.060 |
0.4 (0.3–0.5) |
0.4 (0.3–0.7) |
0.581 |
*The continuous normal distributed variables were described as means and standard deviations. The nonnormally distributed continuous variables were described as medians and interquartile ranges.
M (Q1–Q3): Median (Interquartile 1–interquartile 3); —: Not applicable.
There were no significant differences between the two groups in white blood cell and lymphocyte counts or C-reactive protein levels. Serum amyloid A (SAA) was higher in both groups, but there were no significant differences between the groups. Alanine aminotransferase and creatine kinase levels differed between the two groups but remained within the normal range. In addition, prothrombin time (PT), activated partial thromboplastin time (APTT), and d-dimer levels were shorter in the Delta variant group than in the Omicron variant group. Fibrinogen was higher in the Delta variant group than in the Omicron variant group, but none of these parameters were outside the normal range in either group [Table 2].
There were no significant differences in C-reactive protein, SAA, PT, APTT, fibrinogen, or d-dimer levels between moderate and mild patients in either group [Table 3].
3.4. Comparison of viral shedding time, Ct value, and antibodies
The viral shedding time in the Omicron variant group was shorter than in the Delta variant group, and there was a significant difference between the two groups. There were no significant differences between the two groups in the ORF1ab and N genes Ct values of SARS-CoV-2.
The IgM titer in the Omicron variant group was higher than in the Delta group; however, the median was in the negative range (0-0.79). Simultaneously, the IgG titer of the Omicron variant group was higher than that of the Delta variant group. There was a significant difference between the two groups [Table 4].
Table 4 -
Comparison of viral shedding time, Ct value, and antibodies in the two groups
| Groups |
Viral shedding time, d |
Ct value |
Antibody titer |
| ORF1ab gene |
N gene |
IgM |
IgG |
| Delta variant (n = 109) |
14.0 ± 5.8 |
26.0 (22.0–30.0) |
24.0 (20.5–28.5) |
0.0 (0.0–0.1) |
8.4 (1.0–21.9) |
| Omicron variant (n = 183) |
11.9 ± 5.9 |
25.8 (22.1–33.8) |
22.0 (19.0–31.0) |
0.1 (0.0–0.3) |
24.3 (2.1–162.2) |
|
P
|
0.003 |
0.685 |
0.140 |
<0.001 |
<0.001 |
The continuous normal distributed variables were described as means and standard deviations. The nonnormally distributed continuous variables were described as medians and interquartile ranges.
Ct: Cycle threshold; IgM: Immunoglobulin M; IgG: Immunoglobulin G.
3.5. Comparison of the remission time of chest CT imaging
The time from pneumonia to absorption of lung lesions in the Delta variant group was 13.2 ± 4.2 days, which was longer than in the Omicron variant group, which was 9.0 ± 5.2 days. There was a significant difference between the two groups (P = 0.018).
4. Discussion
Various variants of SARS-CoV-2 have appeared worldwide, especially the Omicron variant B.1.1.529, which contains a large number of mutations in its spike protein, resulting in an ultrahigh transmission rate. In some countries and regions, the number of cases infected by the Omicron variant has exceeded that of Delta and other virus variants within a few weeks, and the global health system is still under tremendous pressure.
This study included 109 patients infected with the Delta variant and 183 patients infected with the Omicron variant from January 19, 2022, to April 1, 2022. During that period, BA.2 has become dominant. For the 110 Omicron strains in this study, three were assigned to the BA.1.1 lineage, 53 were assigned to the BA.2 lineage, and the other 54 were assigned to the BA.2.2 lineage. BA.2 is approximately 4.2 times as contagious as Delta and is also 17-fold more capable than Delta of escaping current vaccines.
The number of patients with moderate disease in the Delta variant group was significantly higher than that in the Omicron variant group. Most of the patients in the Omicron variant group were mild (80%), a small number (13%) were asymptomatic, and only 7% had pneumonia. The remission time of CT imaging in patients with pneumonia was significantly shorter for the Omicron variant than for the Delta variant. In addition, the Omicron variant group had more dry or sore throat symptoms in clinical manifestations. Even older patients or patients with underlying disease or obesity in the Omicron variant group tended to be mild. Our findings were consistent with other reports that the main clinical manifestations of this novel variant are those of a “mild infection.”[5] According to the findings by McMahan,[6] the SARS-CoV-2 Omicron variant may cause a stronger upper respiratory tract infection but a less severe lower respiratory tract clinical disease than previous SARS-CoV-2 variants. Hui et al.[7] discovered that compared with the Delta variant, the Omicron variant was more sensitive to a cathepsin inhibitor but less dependent on TMPRSS2 activity. This implies that the Omicron variant enters the cells mainly via the endocytic pathway, while the Delta variant prefers to fuse at the cell surface. Using a widespread endocytic pathway, the Omicron variant can infect cells expressing ACE2 independently of the presence of TMPRSS2, potentially expanding the cellular spectrum for infection. Cells coexpressing ACE2 and cathepsins are more frequent in the upper airway than cells that coexpress ACE2 and TMPRSS2, which may help explain why Omicron is more capable of replicating itself in the bronchi, according to single-cell sequencing data.[7] Furthermore, Omicron and Delta variants replicated similarly in human nasal epithelial preparations, according to Meng et al.,[8] while Omicron showed decreased replication in lung and gut cells. The Omicron spike protein was less effectively cleaved than the Delta variant. They performed spike-pseudotyped virus experiments to detect variations in replication for effective virus entrance. The increased cellular RNA expression of TMPRSS2 was effectively connected with the impairment in Omicron pseudotyped viral entry into particular cell types, and deletion of TMPRSS2 had a more detrimental effect on the entry of Delta than Omicron.[8] In type I and type II alveolar cells of the lung, TMPRSS2 is substantially expressed, according to single-cell sequencing research.[9] Earlier animal studies have shown more extensive infection of alveolar pneumocytes for the Delta variant, corroborated by the accelerated viral replication of the Delta variant by TMPRSS2.[10] In contrast to the Delta version, Zhao et al.[11] reported that Omicron was inefficient in exploiting TMPRSS2 for viral replication. According to their findings, the Omicron variant may not replicate in the lungs as the Delta variant.[11]
A study by Bojkova et al.[12] showed that the Omicron variant is less effective than the Delta variant in antagonizing the interferon response in human cells, which may explain the reduced pathogenicity of the Omicron variant. According to the study by Evangelos, the “NYNYLYRLF” peptide is an essential amino acid sequence in the RBM region (448–456 positions). This tyrosine (Y)-enriched peptide has 2 contact sites (Y449 and Y453) and is known as the NF9 peptide; in contrast to the Delta variant, the NF9 amino acid content of the Omicron variant remains unchanged, indicating that the NF9 peptide may lead to early activation of the immune system and the release of efficient cytokine, resulting in a faster immunological response and a reduction in SARS-CoV-2 pathogenicity.[13]
In this study, the moderate patients in the Delta and Omicron variants group represented a high proportion of patients 60 years or older, suggesting that old age is still one of the risk factors. At the same time, there were 40 patients 14 years or younger in the Omicron variant group, of which 88% were mild patients, suggesting that unlike other variants, most children still have upper respiratory symptoms. Nyberg et al.[14] discovered strong evidence that the degree of this risk reduction is age-dependent. In individuals older than 20 years, the Omicron variant significantly reduced the incidence of hospitalization compared with the Delta variant. Furthermore, children with Omicron infection may exhibit fever and upper respiratory symptoms more frequently than those with Delta variant infection.[14]
In our study, the number of unvaccinated patients with moderate severity in the Delta variant group was significantly higher than that of mild or asymptomatic patients. In contrast, 80% of patients without pneumonia had been vaccinated with three doses of the vaccine, suggesting that vaccination, especially booster vaccination, still provides substantial protection against Delta variant infection. More than half of the patients in the Omicron variant infection group were not vaccinated or were vaccinated with one or two vaccine doses. According to previous studies, individuals who have received two doses of mRNA vaccines (ChAdOx1 and BNT162b2) or inactivated vaccines (BBIBPCorV) may benefit from the third dose of a booster vaccine against the Omicron variant.[15] A trial showed that for the Omicron variant, the booster vaccine could improve antibody protection by 25 times compared with the two injections of the vaccine, and the antiviral ability after booster is equivalent to the 95% protection provided by the two injections of the vaccine against the original virus strain.[16] Early estimates of vaccine efficacy from several nations indicate that existing vaccines are much less successful against Omicron than Delta and the ancestral virus in two-dose vaccinated individuals, regardless of their previous infection. However, it has been proven that the third booster dose increases antibody levels and helps reverse the downward trend of neutralizing antibodies.[17–21]
In our study, neither group of patients experienced severe or critical illness and most of the laboratory data collected at admission was within the normal range. Prothrombin time, APTT, fibrinogen, and d-dimer levels in both groups were measured at the time of admission without any apparent anomalies. However, fibrinogen levels were higher in the Delta variant group than in the Omicron variant group, while PT, APTT, and d-dimer levels were shorter in the Delta variant group. According to other studies, some COVID-19 patients might have lower PT and APTT, which may be associated with acute inflammatory conditions. These individuals may have milder disease manifestations or be in earlier stages. Elevated d-dimer levels, prolonged PT, and APTT may indicate severe COVID-19 infection with a poor prognosis.[22–24]
Our findings revealed that SAA levels were slightly increased in both groups. Serum amyloid A is a protein produced by hepatocytes in response to proinflammatory cytokines during viral infection. A recent study indicates that SAA may be a valuable indicator of disease severity in COVID-19 patients; decreasing levels of SAA were related to a better prognosis than patients with an ascending trend. In addition, patients with initially elevated SAA levels were more likely to have poor chest imaging.[25]
Our study has several limitations. Because of the small sample size, the age distribution of patients with the Delta variant differed from that of the Omicron group, with a higher proportion of patients aged 14 years in the Omicron group. Therefore, statistical analysis of patients younger than 14 years may not be adequate for comparison. In future work, we will expand the number of patients, match the two groups’ underlying personal conditions, and then compare them. Consequently, additional research and clinical assessment of cohort studies are required.
Acknowledgments
We thank all physicians who participated in the management of these COVID-19 cases.
Funding
This study was supported by the Chang Jiang Scholars program (2019077).
Author Contributions
Zhihai Chen conceived and designed the study. Zhihai Chen and Peng Yang supervised the data collection. Di Tian, Yang Pan, Ziruo Ge, Xiangjing Kong, Yao Zhang, Qing Zhang, and Aibin Wang interpreted the data. Di Tian did the statistical analysis. Di Tian, Yang Pan, and Ziruo Ge prepared the manuscript. Di Tian wrote the manuscript. Di Tian and Ziruo Ge prepared the figures. Yang Pan and Peng Yang performed the COVID-19 specimen processing and sequencing. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity. Zhihai Chen and Peng Yang are the guarantors.
Conflicts of Interest
None.
Data Availability Statement
The sequences generated during the current study are available in the GISAID, with reference no. EPI_ISL_13858946 to EPI_ISL_13858901.
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