Long COVID in a highly vaccinated but largely unexposed Australian population following the 2022 SARS‐CoV‐2 Omicron wave: a cross‐sectional survey

To estimate the prevalence of long COVID among Western Australian adults, a highly vaccinated population whose first major exposure to the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was during the 2022 Omicron wave, and to assess its impact on health service use and return to work or study.

T he severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID- 19), has caused considerable morbidity and mortality around the world.][3][4] A precise clinical definition is difficult: the condition can include a variety of respiratory, neurological, cardiovascular, gastrointestinal, and other symptoms, 5 and differences in the number and duration of symptoms required by various case definitions confound comparisons of long COVID studies. 6,7The World Health Organization therefore developed a clinical case definition of the post COVID-19 condition as "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation." 8,9stern Australia was largely free of locally acquired COVID-19 until interstate and overseas travel restrictions were relaxed in late February 2022, by which time more than 90% of the vaccineeligible population had been vaccinated. 10Western Australia was unusual in that almost all cases of COVID-19 during 2022 were caused by the Omicron variant of SARS-CoV-2 circulating in a population without background immunity acquired during extensive exposure to earlier viral variants. 10,11Consequently, estimates of the risk of long COVID based on experience elsewhere may not be applicable in Western Australia.
The aim of our study was therefore to estimate the prevalence of long COVID among Western Australian adults, a highly vaccinated population whose first major exposure to SARS-CoV-2 was to its Omicron variant in 2022, and to assess its impact on health service use and return to work or study.

Methods
We undertook a survey of Western Australian residents aged 18 years or older at the time of infection for whom SARS-CoV-2 Main outcome measures: Proportion of respondents with long COVID (ie, reporting new or ongoing symptoms or health problems, 90 days after positive SARS-CoV-2 test result); proportion with long COVID who sought health care for long COVID-related symptoms two to three months after infection; proportion who reported not fully returning to previous work or study because of long COVID-related symptoms.

Conclusion: Ninety days after infection with the Omicron SARS-
CoV-2 variant, 18.2% of survey respondents reported symptoms consistent with long COVID, of whom 38.7% (7.1% of all survey respondents) sought health care for related health concerns two to three months after the acute infection.

The known:
The estimated prevalence of long COVID varies widely between studies (range, 9-81% of people with SARS-CoV-2 infections).
The new: In a highly vaccinated population not broadly exposed to earlier SARS-CoV-2 variants, 18% of people infected with the Omicron variant reported symptoms consistent with long COVID 90 days after infection; 18% of these people had not fully resumed previous work or study by three months, and 38% required care from general practitioners for their symptoms two to three months after infection.

The implications:
Long COVID affects a considerable number of people in Australia, and general practices play a major role in managing its burden.
Research infections, detected by polymerase chain reaction (PCR) testing or with rapid antigen tests (RATs), were reported to the Western Australia Department of Health during 16 July -3 August 2022 (recruitment ended once the minimum target of 20 000 participants was achieved), and who had consented during the case review process to follow-up contact for research purposes.We did not include people for whom more than one SARS-CoV-2 infection was recorded, as prior or subsequent infections may influence the likelihood of long COVID (eg, partial immunity conferred by a previous infection).During 14 October -1 November 2022, the Department of Health sent each eligible person a text message with a unique link to the online survey 90 days after their positive SARS-CoV-2 test result.One or two reminder messages were sent to people who did not respond within 24

Survey
Our survey (Supporting Information, part 1) included validated questions from a published questionnaire 13 or derived from WHO and Centers for Disease Control resources. 3,8A pilot study assessed practical aspects of participants completing the online survey (results not reported), and training was provided to staff involved in interviews to standardise data collection procedures.

Outcome measures
The first major outcome was the proportion of respondents with long COVID, defined as their reporting new or ongoing symptoms or health problems, 90 days after a positive SARS-CoV-2 test, that the respondent related to COVID-19.The WHO long COVID definition 8,9 was the basis of our case definition, but we did not require that symptoms be present for at least two months, as symptoms reported three months after infection were presumed to be long standing symptoms.Further, we asked respondents whether they believed their symptoms were related to COVID-19 without enquiring whether other explanations were possible.The purpose of both deviations from the case definition was to ease interpretation of the survey questions for participants.
The second major outcome was the proportion of respondents with long COVID who sought health care for long COVID-related symptoms in the month preceding the survey; that is, two to three months after infection.The third outcome was the proportion of respondents who worked or studied prior to their infection who reported not fully returning to work or study because of long COVID-related symptoms.

Statistical analysis
Sampling weights were calculated using gender and 10-year age groups to adjust for differences in age-gender group proportions between respondents and all Western Australian adults with reported SARS-CoV-2 infections during the study period (Supporting Information, table 1).We report results as weighted proportions with 95% confidence intervals (CIs).
Relationships between variables potentially associated with long COVID and outcomes were assessed in log-binomial regression analyses adjusted for all other variables; we report adjusted relative risks (aRRs) with 95% CIs.The characteristics deemed to be potentially associated with having long COVID were gender, age group, area of residence (metropolitan Perth or other Western Australia) (all obtained by the WA Department of Health during the SARS-CoV-2 notification process), and the Research number and time of COVID-19 vaccinations at least one week before the positive SARS-CoV-2 test (vaccination data recorded in PHOCUS), as well as having a health condition prior to COVID-19 (survey question).When gender was not recorded in the case review database, it was imputed when possible using the gender package in R 4.2.1 (R Core Team), based on first names and United States census data for 1950-2005. 14All other statistical analyses were performed in Stata 15. ◆

Ethics approval
The study was approved by the Western Australia Department of Health Human Research Ethics Committee (RGS0000005516).

Results
Of

Health service use by people with long COVID
Health service use in the month preceding the survey regarding symptoms respondents linked with their COVID-19 illness was reported by 825 people with long COVID (38.7%); 814 visited general practitioners (38.2%), 84 visited emergency departments (3.9%), and 34 were admitted to hospital (1.6%).The adjusted risk of health service use was higher for women than men (aRR, 1.2; 95% CI, 1.1-1.4)(Box 6).

Return to work or study
Of the 1779 respondents with long COVID who had worked or studied before their positive SARS-CoV-2 test, 1154 (64.9%) had returned to work or study within one month of the test result, and a further 307 (17.3%) had returned within 90 days; 271 (15.2%) had reduced the number of hours they worked or studied, and 48 (2.7%) had not returned at all (Box 8).After adjusting for other participant characteristics, the risk of not returning or reduced hours was greater for people who had received two or fewer doses of COVID-19 vaccine than for those who had received four or more doses (aRR, 2.0; 95% CI, 1.2-3.2); the risk was also greater for people with preexisting health conditions (aRR, 1.3; 95% CI, 1.1-1.6)(Box 9).

Discussion
The aim of our survey was to estimate the prevalence of long COVID in a highly vaccinated population exclusively exposed

Research
to the Omicron variant of SARS-CoV-2.We found that 18.2% of respondents met our criteria for long COVID 90 days after a positive SARS-CoV-2 test result, of whom 38.7% had used health services two to three months after their infection because of ongoing symptoms.Among respondents with long COVID who had worked or studied prior to their infection, 15.2% had reduced their number of hours, and 2.7% had not returned to work or study at all.
The prevalence of long COVID in our sample was higher than reported by large studies in the United Kingdom (5-17%) [15][16][17] and Canada (17%), 18 and by a 2022 review of Australian data (9.7% twelve weeks or longer after suspected COVID-19). 19Our finding is, however, lower than that of a recent Queensland study, which found that 21% of people reported ongoing symptoms twelve weeks after PCR-confirmed infections with the SARS-CoV-2 Omicron variant. 20Despite reports that the risk of long COVID may be lower following Omicron infections than with earlier SARS-CoV-2 variants, 18,21 we found that the burden of long COVID may be substantial 90 days after Omicron infections.
About 39% of respondents with long COVID had used health care for ongoing symptoms 60-90 days after SARS-CoV-2 infections, similar to the proportion reported in Switzerland, where 40% of people had at least one contact with the health care system for reasons related to earlier COVID-19. 22This was equivalent to 7.1% of all survey respondents; extrapolated to the 1.2 million people with first SARS-CoV-2 infections reported in Western Australia during 2022, 23 this equates to about 80 000 health care episodes.As more than 90% of health care visits were to general practitioners, and the need for hospital services was quite limited, providing care to people with long COVID could focus on primary care.
We found that 64.9% of respondents with long COVID who were working or studying at the time of their SARS-CoV-2 infection had fully resumed this activity within a month of their test result.However, 17.9% could not do so by 90 days, or had reduced their work or study hours.Long COVID may therefore have economic and workforce implications, as also suggested by other authors. 24nally, we found that the risk of long COVID-related symptoms was lower for people who had been vaccinated against COVID-19, also as reported by other investigators. 256][17][18][19] Nevertheless, differences in access to health care services and unemployment and social welfare support may prevent applying some of our findings outside Australia.

Limitations
To

Conclusion
About 18% of survey respondents from a highly vaccinated population whose first epidemic encounter with SARS-CoV-2 was with its Omicron variant reported symptoms consistent with long COVID 90 days after infection.Hospital-based care was not required by most people, but about 38% of people with long COVID (6.7% of all infected people) had visited general practices two to three months after infection for symptoms they linked with their SARS-CoV-2 infection.Most people with long COVID had fully returned to work or study within a month of their infection, but about 18% had not done so three

2 Characteristics of adult Western Australian residents with reported SARS-CoV-2 infections during 16 July -3 August 2022 who were invited to complete our long COVID survey, 14 October -1 November 2022
COVID-19 = coronavirus disease 2019; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. * Information on pre-existing health conditions was collected for the survey and is therefore not available for people who did not respond to the survey.During the study period, 171 people invited to complete the survey were admitted to hospital (0.7%; source: author Paul Knight [Public Health Operations, Western Australia Department of Health], 20 July 2023).◆

3 Long COVID (90 days after acute SARS-CoV-2 infection, 16 July -3 August 2022) in adult Western Australian residents who responded to our long COVID survey, 14 October - 1 November 2022: log-binomial regression analysis Risk ratio (95% confidence interval)
the 70 876 adults with SARS-CoV-2 infections reported to the Department of Health during 16 July -3 August 2022, 24 024 consented to contact for research purposes (33.9%).We excluded 1280 people from our survey (5.3% of those who provided consent): 912 because more than one SARS-CoV-2 infection had been reported, 342 were not Western Australia residents, and 26 had died prior to the survey.

6 Health service use by adult Western Australian residents with long COVID who responded to our long COVID survey, 14 October - 1 November 2022: log-binomial regression analysis Characteristic Any health service use: risk ratio (95% confidence interval)
COVID-19 = coronavirus disease 2019; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. * Weighted numbers and proportions of respondents.† For all other listed characteristics.◆

8 Return to work or study by adult Western Australian residents who responded to our long COVID survey, 14 October -1 November 2022, by long COVID status: proportions with 95% confidence intervals*
26searchthe likelihood that substantial numbers of unrecognised earlier infections affected background immunity and consequently the development of long COVID after re-infection.However, our findings are based on subjective symptom reports, and the specificity of the selected symptoms for diagnosing long COVID is unclear.As we surveyed only SARS-CoV-2-positive people who had consented to follow-up contact, we could not compare them with a control group without antecedent SARS-CoV-2 infections.Information on health service use and the impact of symptoms on work or study relied on respondents' reports and were not independently verified.Information on the severity of the COVID-19 illness associated with individual SARS-CoV-2 infections was limited to whether they were symptomatic infections; the overall number of hospitalisations (ie, for any cause) of people invited to participate, however, was only 0.7% (Box 2, footnote).Finally, selection and response biases inherent to our study design may have inflated the proportion of people we classified as having long COVID.As the vast majority of notified SARS-CoV-2 infections in Western Australia during 2022 were for people with symptoms, our denominators do not include a potentially large number of asymptomatic or undetected infections (ie, in people who were not tested).Further, people who feel ill are generally more likely to participate in research, and people with ongoing symptoms more likely to complete our survey,26leading to overestimation of the prevalence of long COVID.

9 Adult Western Australian residents with long COVID who responded to our long COVID survey, 14 October -1 November 2022, who had not returned to previous level of study or work: log-binomial regression analysis Risk ratio (95% confidence interval) Characteristic Not returned or reduced hours of work or study* Unadjusted Adjusted †
Researchmonths after their infections.Further studies could enhance our understanding of the duration and severity of long COVID and help identify effective treatment.We are currently assessing the responses to a six-month follow-up survey of the participants in our first survey.