Excess risk and clusters of symptoms after COVID-19 in a large Norwegian cohort

Abstract

Physical, psychological and cognitive symptoms have been reported as post-acute sequelae for COVID-19 patients but are also common in the general uninfected population. We aimed to calculate the excess risk and identify patterns of 22 symptoms up to 12 months after COVID-19. We followed more than 70,000 adult participants in an ongoing cohort study, the Norwegian Mother, Father and Child Cohort Study (MoBa) during the COVID-19 pandemic. Infected and non-infected participants registered presence of 22 different symptoms in March 2021. One year after infection, 13 of 22 symptoms were associated with SARS-CoV-2 infection, based on relative risks between infected and uninfected subjects. For instance, 17.4% of SARS-CoV-2 infected cohort participants reported fatigue that persist 12 months after infection, compared to new occurrence of fatigue that had lasted less than 12 months in 3.8% of non-infected subjects (excess risk 13.6%). The adjusted relative risk for fatigue was 4.8 (95% CI 3.5-6.7). Two main underlying factors explained 50% of the variance in the 13 symptoms. Brain fog, poor memory, dizziness, heart palpitations, and fatigue had high loadings on the first factor, while shortness-of breath and cough had high loadings on the second factor. Lack of taste and smell showed low to moderate correlation to other symptoms. Anxiety, depression and mood swings were not strongly related to COVID-19. Our results suggest that there are clusters of symptoms after COVID-19 due to different mechanisms and question whether it is meaningful to describe long COVID as one syndrome.

Keywords: COVID-19; MoBa; Post-acute sequelae; SARS-CoV-2; The Norwegian Mother, Father and Child Cohort Study.

Fig. 1

Flow chart of MoBa participants

Fig. 2

Incident cases of COVID-19 in the study sample, per month. The first registration of a COVID-19 diagnosis in our dataset was March 6th, 2020. We defined two waves of increased infection rates; March and April 2020 (Wave-1) and September 2020 to January 2021 (Wave-2). Symptoms were reported by all study participants in a questionnaire distributed March 2nd, 2021

Fig. 3

Bivariate tetrachoric correlations between symptoms reported in March 2021 among COVID-19 cases in Wave-1 (11–12 months prior to reporting symptoms) and Wave-2 (1–6 months prior to reporting symptoms). Rare occurrences (kidney disease, myocarditis, fever, hair loss) were omitted. The strength of correlation coefficients are indicated by the colour panel (right). Intensity of red colours indicate increasing negative correlation coefficients, while intensity of blue colours indicate increasing positive correlation coefficients. Correlation coefficients are found in Supplementary Table 7. Asterisks indicating significant correlations (*** for p < .001; ** for p < .01; * for p < .05)