Comparison of the clinical and virological characteristics of SARS-CoV-2 Omicron BA.1/BA.2 and omicron BA.5 variants: A prospective cohort study

•Data about symptoms and viral kinetics of omicron BA.5 is lacking.•We thus compared the symptoms and viral kinetics between SARS-CoV-2 omicron BA.1/BA.2 and omicron BA.5.•Patients with omicron BA.5 had more severe initial symptoms but exhibited shortened viable viral shedding period than those with omicron BA.1/BA.2.•This finding provides evidence for the current CDC guideline about isolation period for patients with SARS-CoV-2 in omicron BA.5 era. Dear editor, A recent study showed SARS-CoV-2 shedding kinetics as the Omicron variant BA.1 emerged.1Kandel C. Lee Y. Taylor M. Lanes A. McCready J. et al.Viral Dynamics of the SARS-CoV-2 Omicron Variant among household contacts with 2 or 3 COVID-19 vaccine doses.J Infect. 2022; 85: 666-670Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar However, the data about viral kinetics and its relation with symptom dynamics in patients with breakthrough infection with different Omicron sublineages are limited, although the Omicron BA.5 have outcompeted the previous variant of concerns of SARS-CoV-2 with several advantages and frequently causes breakthrough infection.2Tegally H. Moir M. Everatt J. Giovanetti M. Scheepers C. Wilkinson E. et al.Emergence of SARS-CoV-2 omicron lineages BA.4 and BA.5 in South Africa.Nat Med. 2022; 28 (2022/09/01): 1785-1790Crossref PubMed Scopus (243) Google Scholar Herein, we provide the data about comparing viral kinetics and symptom dynamics regarding to different Omicron sublineages, BA.1/2 and BA.5. This prospective cohort study included healthcare workers (HCWs) with positive SARS-CoV-2 infection test results from January 14, 2022, to August 3, 2022. All participants were instructed to record daily symptoms based on a 5-score that comprised 24 symptoms and to store daily saliva samples. After the end of the isolation period, every participant submitted the stored saliva samples and records of their symptoms. Genomic and subgenomic RNA viral copy number assessments were performed to those samples, and virus culture was performed on samples with positive PCR results. Statistical analysis and detailed methods of identification of SARS-CoV-2 sublineages, RT-PCR and virus culture were described in supplemental materials. A total of 82 HCWs consented to participate in the study. The baseline characteristics of the remaining 82 participants are shown in Table 1. Among the 82 participants, 40 (48%) were infected with Omicron BA.1 or BA.2, whereas the remaining 42 (52%) were infected with Omicron BA.5 variant. Data on the prevalence of symptoms during the isolation period between the two groups are shown in Table 1 and Figure S1. Overall, compared to participants with Omicron BA.1/2, participants with Omicron BA.5 were more likely to have fever (39% vs. 88%, P<0.001), chills (41% vs. 68%, P = 0.03), myalgia (54% vs. 88%, P = 0.007), and headache (47% vs. 73%, P = 0.03). The proportion of patients with moderate or severe symptoms (symptom score ≥ 2) between the two groups is shown in Table S1. Fever (21% vs. 71%, P<0.001), chills (28% vs. 56%, P = 0.03), fatigue (46% vs. 73%, P = 0.03), myalgia (36% vs. 68%, P = 0.01), headache (21% vs. 51%, P = 0.01), anorexia (8% vs. 30%, P = 0.03), and sore throat (49% vs. 76%, P = 0.03) with a symptom score ≥ 2 were more common among participants with Omicron BA.5.Table 1Baseline characteristics of the participants.Total (N = 82)BA.1 or BA.2 (N = 40)BA.5 (N = 42)P-valueAge, years (mean ± SD)32.0 ± 8.330.4 ± 6.733.4 ± 9.50.10Female64 (79)30 (75)34 (81)0.701st booster75 (94)36 (90)40 (98)0.34Vaccine type0.22- AA3 (4)3 (8)0 (8)- AAP62 (78)32 (80)31 (76)- MM2 (3)1 (3)1 (2)- MMM6 (8)1 (3)5 (12)- MMP1 (1)1 (3)0- PPP6 (8)2 (5)4 (10)Days from last vaccination (mean ± SD)184.7 ± 71.4130.8 ± 67.0234.7 ± 21.5<0.001Initial severity0.02Asymptomatic15 (19)12 (31)3 (7)Mild67 (82)28 (70)39 (93)Proportion of participants with symptomsFever51 (63)15 (39)36 (88)<0.001Chill44 (55)16 (41)28 (68)0.03Fatigue66 (83)30 (77)36 (88)0.32Myalgia56 (70)21 (54)35 (85)0.007Headache48 (60)18 (46)30 (73)0.03Dizziness27 (34)9 (23)18 (44)0.08Rash4 (5)2 (5)2 (5)>0.99Anorexia38 (48)16 (41)22 (55)0.36Conjunctival injection4 (5)3 (8)1 (3)0.57Cough77 (96)36 (92)41 (100)0.22Sputum70 (88)31 (80)39 (95)0.08Sore throat69 (86)30 (77)39 (95)0.07Rhinorrhea57 (72)28 (72)29 (73)>0.99Nasal congestion57 (71)27 (69)30 (73)0.89Dyspnea12 (15)4 (10)8 (20)0.40Chest pain8 (10)4 (10)4 (10)>0.99Ageusia22 (27)9 (23)13 (32)0.54Anosmia24 (30)13 (33)11 (27)0.70Nausea16 (20)6 (15)10 (25)0.47Dyspepsia18 (23)6 (15)12 (30)0.22Vomiting7 (9)3 (7)4 (10)>0.99Diarrhea17 (21)7 (18)10 (24)0.67Constipation2 (3)1 (3)1 (2)>0.99Abdominal pain7 (9)1 (3)6 (15)0.13Day of first sample, (mean ± SD)2.7 ± 1.13.1 ± 1.32.4 ± 0.80.003Number of samples, (mean ± SD)4.0 ± 1.23.9 ± 1.34.1 ± 1.10.41Culture positivity38/302 (13)26/150 (17)12/152 (8)0.01NOTE. Data are presented as number (%) unless otherwise indicated.Abbreviations: A, Astrazeneca ChAdOx1 nCoV-19; P, Pfizer BNT162; M, Moderna.mRNA-1273; SD, standard deviation. Open table in a new tab NOTE. Data are presented as number (%) unless otherwise indicated. Abbreviations: A, Astrazeneca ChAdOx1 nCoV-19; P, Pfizer BNT162; M, Moderna.mRNA-1273; SD, standard deviation. The dynamics of the mean of the total, systemic, respiratory, gastrointestinal, and sensory symptom scores according to the Omicron variant are described in Figure S2 and Figure S3. In both the Omicron BA.1/BA.2 and BA.5 groups, the mean symptom scores peaked around 1–2 days after the onset of symptoms, except for sensory symptom scores (ageusia and anosmia), which peaked around 4–5 days after the onset of symptoms. However, differences in the symptom dynamics between the two groups were not significant, except for the systemic symptoms (fever, myalgia, fatigue, headache, chills, dizziness, and chest pain) on day 0, which showed higher symptom scores in the Omicron BA.5 group (median symptom score 2.7 ± 5.6 vs. 7.3 ± 4.8, P = 0.046). The overall distribution of samples according to the viral copy number, culture positivity, and days after symptom onset is shown in Figure S4 and Table S2. When comparing the genomic viral loads of both the variants between days 4–7 after symptom onset, patients in the Omicron BA.5 group had lower genomic viral copy numbers than those in the Omicron BA.1 and BA.2 group (Day 4, 5.1 ± 1.6 vs. 4.3 ± 1.8, P = 0.045; Day 5, 4.6 ± 1.5 vs. 3.4 ± 2.1, P = 0.009; Day 6, 4.4 ± 1.7 vs. 3.0 ± 2.5, P = 0.02: Figure S3). However, in both the groups, the generalized mixed model analysis revealed that the viral load decreased over time (P for group effect <0.001), while the viral loads were not significantly different between the two groups (P for group effect =0.60). Survival analysis revealed insignificant differences in genomic and subgenomic RNA clearance between the two groups (P = 0.73 in the log-rank test for genomic RNA clearance: Figure 1A; P = 0.61 in the log-rank test for subgenomic RNA clearance: Fig. 1B). On the other hand, Omicron BA.5 was associated with a shorter viable virus shedding period than Omicron BA.1 or BA.2 (median 2.5 days, IQR [2–3] vs. median 4 days, IQR [3–5], P<0.001: Fig. 1C). A previous study reported that the proportion of asymptomatic patients infected with the Omicron variants was around 20%.3Garrett N. Tapley A. Andriesen J. Seocharan I. Fisher L.H. Bunts L. et al.High asymptomatic carriage with the omicron variant in South Africa.Clin Infect Dis. 2022; 75: e289-e292Crossref PubMed Scopus (26) Google Scholar In contrast to this finding, our study observed that all the participants, even those who were initially asymptomatic, eventually developed symptoms during the isolation period. The most notable difference in the symptom dynamics between the two groups was that the systemic symptoms were more common and severe in the BA.5 group at the time of onset of symptoms. However, the severe systemic symptoms in HCWs with BA.5 might be a reflection of waning vaccine-induced immunity.4Boulware D.R. Murray T.A. Proper J.L. Tignanelli C.J. Buse J.B. Liebovitz D.M. et al.Impact of SARS-CoV-2 vaccination and booster on COVID-19 symptom severity over time in the COVID-OUT trial.Clin Infect Dis. 2022; : ciac772Crossref PubMed Scopus (1) Google Scholar Further studies on this topic are needed. In contrast, the Omicron BA.5 variant had a shorter viable virus shedding period than the Omicron BA.1 or BA.2 variant. On 31 August 2022, CDC revised the isolation period for patients with mild COVID-19 to 5 days after the onset of symptoms and recommends the use of a high-quality mask until day 10 if the patient is afebrile and symptoms are improving .5Ending Isolation and Precautions for People with COVID-19: interim Guidance [Internet]. Centers for Disease Control and Prevention. 2022 [cited December 26, 2022]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html.Google Scholar The present study observed that viable viruses were detected for up to 6 days in patients infected with Omicron BA.1 or BA.2 and up to 5 days in those with the Omicron BA.5 variant. These findings are consistent with the current CDC recommendations. In conclusion, we found that the Omicron BA.5 variant was associated with more severe and frequent systemic symptoms, while a shorter viable virus shedding period was observed among HCWs infected with the BA.5 variant than those infected with the BA.1/BA.2 variant. Our findings support the current CDC guidelines for COVID-19 regarding isolation and precautions. This study was supported by grants from the research fund donation for COVID-19 research to Asan Medical Center by Kyu-Kang Cho, the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which is funded by the National Institute of Infectious Diseases, National Institute of Health, Republic of Korea (grant No. HD22C2045), and the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT, Republic of Korea (NRF-2022M3A9I2017241).