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Study describes the symptom profiles of the main variants of SARS-CoV-2

In a recent study posted to the medRxiv* preprint server, researchers assessed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant-specific coronavirus disease 2019 (COVID-19) symptoms among residents of England.

SARS-CoV-2-positive patients exhibit a wide range of symptoms, that differ among patients based on the causative SARS-CoV-2 variant. The identification of high-risk individuals to acquire SARS-CoV-2 infections or transmit SARS-CoV-2 by their symptom profiles would benefit the population as healthcare authorities and governments have started to lift COVID-19 restrictions.

Study: Variant-specific symptoms of COVID-19 among 1,542,510 people in England. Image Credit: Fit Ztudio/Shutterstock

The REaltime Assessment of Community Transmission-1 (REACT-1) study has tracked the prevalence and transmission of SARS-CoV-2 infections and their clinical manifestations among the general population of England between May 1, 2020, and March 31, 2022.

About the study

In the present study, researchers assessed the SARS-CoV-2 variant-specific COVID-19 symptoms among the English population.

COVID-19 symptomatology of the REACT-1 study participants was analyzed of the following SARS-CoV-2 strains: wild-type, Alpha (B1.1.1.7), Delta (B.1.617.2), Omicron BA.1 (B.1.1.529.1), and Omicron BA.2 (B.1.1.529.2) and the symptoms that correlated with higher viral loads (or infectiousness) were identified for every variant. The REACT-1 study participants filled out a questionnaire (telephonic or online) on their demographic and symptom details and self-collected their oropharyngeal and nasopharyngeal swab samples for polymerase chain reaction (PCR) tests.

A total of 26 probable COVID-19                symptoms were enlisted, and the respondents mentioned if they developed any of the symptoms in the week prior to their PCR tests. The symptom list included change or loss of taste or smell, pulmonary/cardiovascular symptoms, cold- and influenza-like symptoms, gastrointestinal symptoms, fatigue symptoms, and others.

For the analysis, data of 15 REACT-1 study rounds conducted between June 19, 2020, and March 31, 2022, were analyzed. Rounds 2 to 7 were conducted between June 19, and December 3, 2020, during wild-type strain predominance; rounds 8 to 10 were conducted between January 6, and March 29, 2021, during Alpha predominance; rounds 13 to 15 were conducted between June 24 and November 5, 2021, during Delta predominance; and the rounds 17 to 19 were conducted between January 5 and March 31, 2022, during Omicron predominance.

Data from a few rounds (1, 11, 12, 16) were excluded from the analysis since the questions of round 1 were inconsistent with subsequent rounds, and the other rounds (11, 12, and 16) were conducted when two variants were competing for predominance.

Furthermore, the symptom severity of Omicron BA.1 and Omicron BA.2 infections was assessed among swab-positive participants who were booster (triple) vaccinated 14 days prior to the PCR tests. Lastly, the association between nucleocapsid (N) gene, cycle threshold (Ct) value, and the symptom profiles were evaluated in swab-positive participants of rounds 17 to 19 (Omicron predominance). Logistic regression models and odds ratios (OR) were used for estimating the risk of PCR swab positivity and comparing the variant-wise symptom profiles.


The final analysis comprised 17,448 PCR or swab-positive participants, of which 0.4%, 0.6%, 0.7%, and 4% were infected with wild-type, Alpha, Delta, and Omicron, respectively. Most swab-positive participants who reported the enlisted COVID-19 symptoms had BA.2 infections (76%) in comparison to those infected with Omicron BA.1 (70%), Delta (64%), Alpha (55%), and wild-type (45%) strains.

The highest COVID-19 symptom prevalence among the participants was observed from January to March 2022 during Omicron predominance (22%). Omicron BA.2-infected participants reported a mean of six symptoms a week prior to the PCR tests, higher than the number of symptoms (n) reported due to infections with wild-type (2.7), Alpha (3.4), Delta (4.6), and Omicron BA.1 (4.6). Further, a higher number of BA.2-infected participants (18%) mentioned that their COVID-19 symptoms substantially affected (‘a lot’) their ability to perform daily activities in comparison to any other variant infections.

All the reported COVID-19 symptoms correlated with swab (PCR) positivity for all SARS-CoV-2 variants. The ORs for swab positivity and symptom correlation were highest for Omicron BA.2 infections (OR=13) in comparison to those by wild-type (5.2), Alpha (6), Delta (9.5), and Omicron BA.1 (9.6) infections. For Delta, Alpha, and wild-type strains, the highest swab positivity ORs observed were for change/loss of smell (ORs 73, 38, and 50, respectively) or change/loss of taste (ORs 68 39, and 36, respectively).

Contrastingly, for Omicron BA.1 and Omicron BA.2 variants, cold-like and influenza-like symptoms better predicted swab positivity; the highest symptom ORs observed were of fever: ORs 18 and 30 for BA.1 and for BA.2, respectively in comparison to 13 and 17, respectively for change/loss of smell, and 16 and 21, respectively change/loss of taste. Positive associations were observed between BA.2 infections and COVID-19 symptoms such as severe fatigue, chest pain, muscle aches, runny nose, tiredness, sneezing, chills, fever, tiredness, headaches, and blocked nose.

Among the booster-vaccinated participants, BA.2-infected participants showed a 64% higher probability of reporting COVID-19 symptoms that substantially interfered (‘a lot’) with their daily activity performance. Further, males showed 40% less probability of reporting COVID-19 symptoms that substantially interfered (‘a lot’) with their daily work. The Ct values were lower among Omicron BA.2-infected and symptomatic participants than BA.1-infected and asymptomatic participants. For Omicron infections (rounds 17 to 19), patients who reported more COVID-19 symptoms demonstrated lower Ct scores.

Overall, the study findings highlighted variant-wise symptom profiles of SARS-CoV-2 infections and a change in the association between symptom reporting and Ct scores for Omicron infections.

*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.

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