How do symptom burden and viral kinetics differ between healthy, vaccinated adults infected with either Delta, Omicron BA.1, or BA.2?

In a recent study posted to the medRxiv* preprint server, researchers assessed the symptom profiles present in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta, Omicron BA1. and BA.2-infected patients.

Study: Non-hospitalised, vaccinated adults with COVID-19 caused by Omicron BA.1 and BA.2 present with changing symptom profiles compared to those with Delta despite similar viral kinetics. Image Credit: Naumova Marina/Shutterstock
Study: Non-hospitalised, vaccinated adults with COVID-19 caused by Omicron BA.1 and BA.2 present with changing symptom profiles compared to those with Delta despite similar viral kinetics. Image Credit: Naumova Marina/Shutterstock

Background

Coronavirus disease 2019 (COVID-19) vaccines have played an important role in curbing the transmission of SARS-CoV-2 infections. However, the waning of vaccine efficacy due to novel SARS-CoV-2 variants of concern (VOCs) that effectively evade the immune system has limited the impact of these vaccines on the pandemic.

About the study

In the present study, researchers compared the symptom profile and viral kinetics observed between healthy and vaccinated individuals infected with either SARS-CoV-2 Delta, Omicron BA.1, or BA.2 based on the number of vaccine doses received.

The team conducted a fourth analysis for the Legacy study cohort that assessed symptoms as well as viral load corresponding to Delta, Omicron BA.1, and BA.2 infections after the receipt of two or three COVID-19 vaccine doses. The team noted the data for the analysis on 16 May 2022. The participants underwent either weekly or biweekly health testing to detect COVID-19. The participants were recruited after a COVID-19 vaccine dose or a positive COVID-19 test.

All infected participants diagnosed with COVID-19 either via symptomatic testing or asymptomatic polymerase chain reaction (PCR) screening provided same-day swabs for up to 10 days. One swab was collected between 11 and 30 days after symptom onset. Symptom severity among non-hospitalized patients was self-reported and classified as asymptomatic, mild, moderate, and severe infections. Furthermore, the team defined symptoms as either grade I that neither interferes with the patient’s daily routine nor requires further procedure; but causes slight discomfort, grade II that interferes with certain aspects of the patient’s daily routine or requires further procedure but is not damaging to health and causes moderate discomfort, and grade IIIthat results in alteration, discomfort or disability which is damaging to health.

The symptoms were also categorized based on symptom profiles into three classes according to COVID-19 symptoms: (1) symptomatic with cardinal symptoms such as cough, anosmia, or fever, (2) symptomatic with only non-cardinal symptoms, and (3) asymptomatic. The team also categorized the symptoms based on updated NHS guidance for triggers to initiate isolation of symptomatic COVID-19 patients: (1) asymptomatic, (2) symptomatic and afebrile, (3) febrile alone, (4) and febrile with other symptoms.

Furthermore, ribonucleic acid (RNA) extraction was performed using the nasopharyngeal swabs collected during breakthrough infection. The viral RNA was subsequently genotyped using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) to confirm COVID-19 infection. 

Results

The study results showed that the team accurately detected the causative SARS-CoV-2 variant in 90% of the infected participants. Based on the variant, the team classified the patient cases into five groups: (1) Delta infection after two vaccine doses (2d+Delta), (2) Delta after three doses (3d+Delta), (3) Omicron BA.1 after two doses (2d+BA.1), (4) Omicron BA.1 after three doses (3d+BA.1), and (5) Omicron BA.2 following three doses (3d+BA.2).

The team noted that the proportion of asymptomatic infections ranged between 100% in the 3d+Delta group and 13% in the 3d+BA.2 group. However, almost 76% of the participants reported disease severity ranging between grade I and grade II. Moreover, the number of asymptomatic cases among patients diagnosed with BA.1 or BA.2 infections was 28% and 13%, respectively. Notably, the median duration for which the symptomatic patients displayed symptoms was nine days.

The team also observed that anosmia was reported by 7% to 20% of Omicron patients and 41% of 2d+Delta patients. Cough was reported by 45% of the 2d+BA.1 and 39% of the 2d+Delta patients. Furthermore, the proportion of patients who reported fatigue, coryza, myalgia, shortness of breath, fever, and diarrhea was similar across all symptomatic patient cohorts. Moreover, among the 3d+BA.1 patients, 50% experienced one or more cardinal symptoms, 20% were asymptomatic, and 30% had only non-classical symptoms.

Furthermore, the team also noted that 23% of the BA.1 and 37% of the BA.2 infections triggered self-isolation due to the manifestation of fever in adults vaccinated with three COVID-19 vaccine doses.    

Conclusion 

Overall, the study findings showed that the symptomatic profiles of the SARS-CoV-2 VOCs and the changing immunities of the general population have led to the manifestation of varied COVID-19-related symptoms.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Bhavana Kunkalikar

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.

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