In this population-based prospective cohort study, we found that people infected with Omicron had a similar risk of a range of specific post-covid complaints than people infected with Delta, both in the acute (14-29 days ), as in the subacute (30). -89 days) and post-covid chronic phases (≥90 days). However, at 90 days or more after testing positive, individuals with Omicron infection had a lower risk of having no complaints (43 (95% CI = 14-72) fewer per 10,000), as well as a lower risk of musculoskeletal pain (23 (95). % CI = 2-43) less per 10,000) than individuals with Delta infection.
Comparison with previous studies
This is, to our knowledge, the first study to provide estimates of Omicron variant sequelae. As such, it sheds important new light on the growing body of evidence suggesting that Omicron leads to milder acute illness and fewer hospitalizations than Delta4. We found no studies of post-covid medical records in primary care for effective comparison of findings with previous studies of other SARS-CoV-2 variants. Thus, the finding of a similar prevalence of specific post-covid complaints, except for fewer musculoskeletal complaints after 90 days among those infected with Omicron than among those infected with Delta, has not been previously reported. Several studies have been conducted comparing individuals with confirmed COVID-19 (usually for earlier or unspecified variants of SARS-CoV-2) with individuals without confirmed COVID-1910. We could shed new light on these studies by comparing both the putatively milder Omicron variant and the putatively more severe Delta variant, with similar uninfected comparison groups as in previous studies. Like previous studies, for example based on self-reported data or hospital data1,11, we found that the risk of fatigue and shortness of breath was high for those infected compared to those not infected. Here, we could show that the risk elevation is likely independent of the latest SARS-CoV-2 variant Omicron and Delta (in primary care data).
The Omicron and Delta risk of fatigue and shortness of breath relative to the uninfected were highest in the acute and subacute periods post-covid, with no difference after 90 days or more (Fig. 4, Supplementary Fig. 4 ). ). However, when Omicron and Delta were compared to each other, we found small discrepancies in breathlessness estimates from Cox vs Logit regression models. In Cox models, there appeared to be a 20% decrease in the risk of shortness of breath over the 14- to 126-day interval for Omicron vs Delta (Fig. 1). In contrast, logit models showed no difference in absolute risk over the same period (-3 (-7 to 1) cases per 10,000 with Omicron vs Delta). The different findings of the different models may be due to the Cox model including only the first mention in the medical history, whereas the logit models include all records (on average at 1 per week). The Cox model would therefore systematically choose the earliest record of shortness of breath, which we find in Figure 4 , Supplementary Figure 4 and Table 2 clearly rises closer to the test date. It is possible that people with shortness of breath (or other complaints) refrained from contacting the doctor a second time, or that the doctor did not bother to code the same complaint, which could lead to misclassification of complaints towards later study periods. However, unless widespread talk of Covid-19 only leads to behavioral responses among those infected, we expect this time difference misclassification to affect all study groups to the same extent, i.e. it would have a limited impact on our findings. Misclassification bias is a common threat to validity in all registry-based research, and in return, this research can provide a good overview of the health service burden of a disease.
Relevance to public health, the clinic and future research
Overall, our results suggest that included post-covid complaints exist to a similar extent after Omicron infection than after Delta infection, at least for the acute and subacute post-chronic phases. However, we found indications that the Omicron variant might be milder than the Delta variant at 90 days after positive testing and beyond, in studies of any complaint and in studies of musculoskeletal pain. No group differences could be observed at 90 days for post-Covid main post-Covid complaints (fatigue and respiratory complaints) as recently defined by the World Health Organization12 (‘persistent complaints, usually fatigue and difficulty for breathing, with an unknown cause still present at 3 years). months from the start”). Our findings suggest that Omicron and Delta will carry a similar burden of this WHO-defined post-covid fatigue and shortness of breath in the long run, but that there may be fewer visits with any post-covid complaint and fewer visits with musculoskeletal pain. in those infected by Omicron than in those infected by Delta.
Therefore, our findings may have some important combined clinical and public health messages. First, we provide information on the natural clinical history following Omicron vs Delta infection in a population where the majority is vaccinated, demonstrating the need for further study of the onset, duration and severity of post-covid complaints after the Omicron variant, for example, using the patient. – Reported or clinical data. We also provide data material for use by public health workers, policy makers and clinicians, for example, to estimate costs and prioritize resources in primary care at times or regions when many are simultaneously infected with Omicron.
Strengths and limitations
Strengths of our study include the use of sequenced data that allows Omicron and Delta to be compared during the same calendar period when the two variants had the greatest overlap, combined with unworn health record data. In addition, equal access to SARS-CoV-2 testing at no cost to individuals, as well as a universal tax-funded healthcare system, improve the generalizability of findings to other countries.
A limitation of our study is that we could not include antigen or household tests as they were not registered. However, polymerase chain reaction testing was mandatory for everyone with a positive antigen test at the beginning of our study period. In addition, all participants in our study had a PCR test in a period characterized by high uncertainty regarding the severity of the new Omicron SARS-CoV-2 variant. It is possible that our population consisted of particularly health-conscious individuals who were highly likely to get tested and who were more likely to seek medical care after learning that they had been ill. Indeed, there were some important differences in baseline characteristics of health care seeking (testing and health care use) and mortality that may affect our findings through selection/stratification. confounder and/or confounding bias. We believe that our methodological approach that ensures comparison of individuals who were tested during the same calendar week, inclusion of untested and untested + test negatives in sensitivity analyses, as well as adjustment for a range of covariates, including health-seeking behavior, would limit this potential. biases Furthermore, any differential mortality is unlikely to affect our findings, as it was below 0.2% for all study groups.
A second limitation may be that the 10–18% who tested positive after being included with a negative or no test were not representative of the population of origin, introducing differential loss to follow-up. More specifically, knowing that infection with the Omicron variant comprised 80% of individuals on December 31, 2021 (Supplementary Figure 1), increasing further by January 2022, we would also know that nearly all individuals who tested positive after testing negative, he tested positive with the Omicron variant, further reinforcing the loss of dependence at follow-up. Furthermore, with the knowledge that (1) Omicron infection is known to cause a milder initial course of the disease than previous variants4, probably causing less anxiety and less testing in the population, (2) mass vaccination with the third-dose mRNA vaccine occurred in Norway began in January 202213, probably resulting in fewer tests and (3) test criteria became less stringent during the follow-up period14, embracing fewer and, by thus, they resulted in fewer PCR tests but more home/antigen tests (we did not have access to test results). of home tests/antigens), we can infer that only the most severe Omicron cases with some specific features would have a PCR test instead of or in addition to an antigen test during the follow-up period. Censoring these individuals from the date of positive test could violate the assumption of independent censoring, as a participant could be lost to follow-up because one of the outcomes was about to occur. As our primary aim of the study was to compare Omicron and Delta, for which censoring at the positive test was not an issue, we chose to present the proportions of uninfected people who became infected during follow-up, as well as performing analyzes with and without censorship of the observations from the date of their positive test and later15. As expected, the estimates from the analyzes with censoring on the positive test were higher than the estimates from the analyzes without this censoring (Fig. 3 vs Supplementary Fig. 3 and Fig. 4 vs Supplementary Fig. 4). We believe that alternatives to handle dependent censoring, for example imputation16 or inverse probability weighting17, would add unnecessary complexity to our study without contributing to answering our main research question.
A third limitation may be misclassification and data (outcomes) may be underreported and/or underpowered, as briefly described above. For example, we had few observations of brain fog, and the estimates should be interpreted with caution. To address these challenges, we’ve added a result that includes any of the specific complaints, consistently showing up in the top…