key: cord-0314984-gjtss2my authors: Hedley, P. L.; Hoffmann, S.; Lausten-Thomsen, U.; Voldstedlund, M.; Bjerre, K. D.; Hviid, A.; Krebs, L.; Jensen, J. S.; Christiansen, M. title: A nationwide study of Chlamydia trachomatis infections in Denmark during the COVID-19 pandemic date: 2021-07-06 journal: nan DOI: 10.1101/2021.06.30.21259819 sha: e842a0950f83f420e81f496f9d96de2a5afe33c7 doc_id: 314984 cord_uid: gjtss2my Objectives: COVID-19 policies have been employed in Denmark since March 2020. We examined whether COVID-19 restrictions had an impact on Chlamydia trachomatis infections compared with 2018 and 2019. Methods: This retrospective nation-wide Danish observational study was performed using monthly incidences of laboratory confirmed chlamydia cases and number of tests, obtained from nation-wide surveillance data. Additionally, Oxford COVID-19 Government Response Tracker data, and Google COVID-19 Community Mobility Reports were used to contextualise the behavioural adaptions seen as a result of COVID-19 policies. Testing rates were compared using Poisson regression and test positivity rates were compared using logistic regression. Results: The crude incidence rate (IR) of laboratory confirmed chlamydia infections was reduced to 66.5 per 105 during the first (March-April 2020) lockdown period as compared to 88.3 per 105 in March-April 2018-2019, but the testing rate was also reduced (Rate ratio 0.72 95% CI 0.71-0.73), whereas the odds ratio for a positive test between the two periods was 0.98 (95% CI 0.96-1.00). The period of eased COVID 19 restrictions (May-December 2020) and the second lockdown period (December 2020-March 2021) were characterised by marginally increased crude IRs, while the number of tests performed, and test positivity rates returned very close to the levels seen in 2018-2019. These results were independent of sex, age group, and geographical location. Conclusion: The first Danish COVID-19 lockdown resulted in a reduction in the number of chlamydia tests performed and a consequent reduction in the number of laboratory-identified cases. This period was followed by a return of testing and test positivity close to the level seen in 2018-2019. Altogether the Danish COVID-19 restrictions have had negligible effects on laboratory confirmed C. trachomatis transmission. COVID-19 was declared a pandemic on March 11, 2020. 1 In Denmark, a strict lockdown was implemented which restricted workplace and school attendance, while encouraging residents to stay home. 2 COVID-19 restrictions have remained in place, with varying stringency ever since. These restrictions have had a plethora of behavioural and psycho-social effects. 3 Danish COVID-19 restrictions have, as expected, been associated with remarkable reductions in the incidence of infectious diseases such as influenza, and pertussis, as well as invasive meningococcal and pneumococcal infections 4 5 . Perhaps less expected, COVID-19 restrictions have also been associated with a dramatic reduction in extremely preterm birth. 6 This raises the question, could a reduction in infectious disease burden, particularly ascending urogenital infections (UGIs), several of which have been associated with preterm birth, 7 explain the reduction in extremely preterm birth? While we can't answer this question directly, we can assess the incidence of chlamydia within the Danish population as a proxy for transmissible UGIs. In Denmark, chlamydia is the most frequent bacterial sexually transmitted infection (STI), and it has been subject to mandatory laboratory notification since 1994. Additionally, Chlamydia trachomatis infection either co-occurs or shares predisposing risk factors with several UGIs, e.g. bacterial vaginosis 8 or genital mycoplasmas, 9 which makes it a possible surrogate marker for a broader range of, non-notifiable, UGIs. We hypothesized, that the incidence of C. trachomatis infections would reflect behavioural changes induced by the COVID-19 restrictions in Denmark. Using publicly available data originating from The Danish Microbiology Database (MiBa) 10 via the webportal at Statens Serum Institut 11 alongside national surveillance data pertaining to the number of tests performed, 12 we compared the incidence of laboratory verified C. trachomatis infections since the initiation of COVID-19 restrictions with that of the preceding two years, 2018-2019. The incidences were contextualized using lockdown stringency information from the Oxford COVID-19 Government Response Tracker (OxCGRT) 13 14 and mobility data from Google COVID-19 Community Mobility Reports. 15 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Numbers of laboratory confirmed C. trachomatis infections were obtained via extracts from MiBa via the webportal at Statens Serum Institut. 10 11 The monthly number of C.trachomatis laboratory tests performed since January 2018 were obtained from national surveillance data extracted from MiBa 12 . Lockdown stringency data were obtained from OxCGRT. 13 16 Mobile phone-based location data were obtained from Google COVID-19 Community Mobility Reports. 15 With the exception of the national surveillance data, 12 all data were obtained from publicly available sources. We have examined the period since the first containment policies were enacted following the report We describe incidence rates (number of laboratory-confirmed C. trachomatis infections / population at risk on January 1st of the relevant year) according to age, sex, period, and geographical region (province of residence). The number of tests performed is described per month since January 2018. We compare the number of tests performed using Poisson regression, offset by population size to estimate rate ratios (RRs) with 95% confidence intervals (CIs). RRs were adjusted for period (2018-2019, 2020, and 2021). We estimated odds ratios (ORs) with 95% CIs comparing the odds of a positive test result (among all tests) according to period. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 6, 2021. ; https://doi.org/10.1101/2021.06.30.21259819 doi: medRxiv preprint Statistics were conducted using R version 4.0.3. All data were aggregate and most from publicly available sources supplemented with national surveillance data, so approvals from neither scientific ethics committees nor Data Authorities were necessary as per Danish law and regulations. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 6, 2021. ; https://doi.org/10.1101/2021.06.30.21259819 doi: medRxiv preprint The crude incidence rate (IR) of laboratory confirmed chlamydia infection was 66.5 per 10 5 during the first lockdown March-April 2020, as compared to a crude IR of 88.3 per 10 5 in March-April 2018-2019 (Table 1) . However, the adjusted Rate Ratio (aRR) of tests performed in the periods was 0.72 (95% CI 0.71 -0.73), whereas the OR of having a positive test was 0.98 (95% CI 0.96 -1.00) ( The Danish COVID-19 policies are indicated in Figure 1 . The first Danish COVID-19 case was found on February 27, 2020, and this was followed by information campaigns, introduction of testing and contact tracing, travel restrictions, and other containment strategies 17 (Figure 1 ). March 12, 2020, when the number of COVID-19 cases rose dramatically and the WHO declared COVID-19 a pandemic, strict lockdown measures were introduced, with workplace and school closures, as All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 6, 2021. Figure 1 ). This behavioural difference was seen despite a similar level of formal lockdown stringency ( Figure 1) . Thus, the first lockdown period was associated with a reduction in testing for C. trachomatis as well as a reduction in laboratory confirmed chlamydia infections, followed by a relative increase in testing and number of infections between May and December 2020, whereas the second lockdown period was characterised by a marginal increase in the number of tests performed, and a marginal reduction in test positivity (Table 1 & Supplementary Table 1 The chlamydia incidence in the 11 provinces of Denmark is shown in Supplementary Figure 3 . No marked differences in temporal development between provinces were observed, suggesting that the All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 6, 2021. ; https://doi.org/10.1101/2021.06.30.21259819 doi: medRxiv preprint behaviour changes associated with COVID-19 restrictions were uniformly spread throughout Denmark. The ratio between the number of men and women with chlamydia was < 0.6 in persons aged 15 -24 years but increased with age ( Figure 2 ) to > 1 in persons aged 45 -54 years. This picture is compatible with the pre-COVID lockdown epidemiology of chlamydia. 18 However, a decrease in the ratio in March, followed by an increase in April and May 2020, in persons in the age group 45-54 years was noted. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 6, 2021. ; https://doi.org/10.1101/2021.06.30.21259819 doi: medRxiv preprint The first lockdown period was associated with a moderate, ~25 %, decrease in laboratory confirmed C. trachomatis cases (Table 1) . However, this period was also associated with a similar decrease in laboratory tests performed (Table 1 ) and accounting for that showed that in fact there was no change in the odds of receiving a laboratory confirmed chlamydia diagnosis during the first lockdown and the average odds for the same period between 2018 and 2019 ( Table 1 ). This suggests that the decrease in incidence rate is caused by reduced testing. The second lockdown showed a nominal increase in chlamydia cases (Table 1) despite being formally as stringent as the first lockdown ( Figure 1 ). However, the number of tests performed also increased marginally during the second lockdown and after accounting for this there is a small reduction between the odds of receiving a laboratory confirmed chlamydia diagnosis during the second lockdown and the corresponding odds during the same period in 2018-2019. This may suggest that the behavioural response was markedly more relaxed during the second lockdown than during the first lockdown (Supplementary Figure 1) . The period between the lockdowns was associated with a marginal increase in the incidence rate of making it worthwhile considering whether planned or delayed tests were simply done over the following months. Additionally, the statement that "Sex is good, sex is healthy, the Danish Health All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 6, 2021. ; https://doi.org/10.1101/2021.06.30.21259819 doi: medRxiv preprint Authority is in favour of sex", purported broadly by the director of the Danish Health Authority in the Danish media in April 2020 20 may have contributed to a normalisation of sexual behaviours and consequent normalisation of chlamydia cases. It cannot be excluded that the decrease in testing, and consequent decrease in incidence of laboratory confirmed cases, seen in March -April 2020 was caused -at least partly -by reduced sexual activity among teens and young adults during the first lockdown; however, the period also saw a marked increase in online dating internationally, 21 as well as in Denmark. 22 , suggesting that reduced sexual activity was not the explanation. The gender distribution of laboratory-verified cases of chlamydia during the COVID-19 restrictions was similar to that seen the years previously, suggesting that the overall epidemiology was unchanged ( Figure 2 ). Likewise, the temporal variation in chlamydia incidence during the COVID-19 restrictions was neither influenced by gender (Supplementary Figure 2) , nor geographical location (Supplemental Figure 3) . Overall, the Danish COVID-19 restrictions -during the first lockdown -were associated with a decrease in the extent of testing and, consequently, of incidence of laboratory confirmed chlamydia. The COVID-19 restrictions had very little -if any -effect on transmission of chlamydia in Denmark. Similar findings were reported from Finland, where C. trachomatis and Neisseria gonorrhoeae incidence were completely unperturbed during the first five months of the pandemic and lockdown measures. 23 This is in contrast to cities in Italy and Spain, where the number of STIs (both syphilis, gonorrhoea and chlamydia) dropped precipitously during the lockdown. 24 25 However, in Trento, Italy, the number of cases in 2020 was comparable to 2019, and risky sexual behaviour was not reduced. 26 The difference between parts of Italy and Spain and northern Europe may be the extent to which tourism contributes to the incidence of STIs, 24 as well as the extent to which the population follows the recommendations and instructions by the health authorities. In the US, a slightly different pattern was seen, with a decrease in chlamydia of ~20 % compared to 2019, All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 6, 2021. ; https://doi.org/10.1101/2021.06.30.21259819 doi: medRxiv preprint and a smaller decrease in gonorrhoea and an unchanged syphilis incidence. 27 Perhaps the significant reductions in all STIs depend on whether a curfew is part of the lockdown restrictions? The lack of relation between limitations in mobility and social interaction and chlamydia incidence may be a result of the extent to which dating apps were used, particularly important among young adults. 21 28 In conclusion, the first Danish lockdown period was associated with a decrease in testing and a subsequent reduced incidence of laboratory confirmed chlamydia. This was not seen in the second lockdown period and the intervening period of eased restrictions. Thus, the period of COVID-19 restrictions, with its significant effects on behaviour, was not associated with appreciable changes in chlamydia transmission. Figure 1 . The Danish COVID-19 restrictions, the black line represents the overall stringency index, the stacked coloured columns represent the measures of the containment and control policies implemented during the whole COVID-19 restriction period. The coloured lines represent Containment, Economic support, and Government response indices, respectively. Data source for panel B: https://www.bsg.ox.ac.uk/research/research-projects/covid-19-government-response-tracker#data. 13 The black dot-dashed vertical lines define the extent of the two strict lockdown periods. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 6, 2021. ; https://doi.org/10.1101/2021.06.30.21259819 doi: medRxiv preprint All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 6, 2021. ; https://doi.org/10.1101/2021.06.30.21259819 doi: medRxiv preprint WHO. WHO Director-General's opening remarks at the media briefing on COVID-19 -11 Her er regeringens nye tiltag (Denmark is closing down: Here are the government's new initiatives) nyheder.tv2.dk: TV2; 2020 Psycho-social factors associated with mental resilience in the Corona lockdown SSI. Individually notified diseases 2020 Copenhagen /20 influenza season was very unusual Copenhagen, Denmark: Statens Serum Institut Danish premature birth rates during the COVID-19 lockdown Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: US Preventive Services Task Force Recommendation Statement Risk factors for bacterial vaginosis in pregnancy: a population-based study on Danish women The Associations of Genital Mycoplasmas with Female Infertility and Adverse Pregnancy Outcomes: a Systematic Review and Meta-analysis The Danish Microbiology Database (MiBa) 2010 to 2013 Monitoring in numbers, graphs and maps Electronic reporting of diagnostic laboratory test results from all healthcare sectors is a cornerstone of national preparedness and control of COVID-19 in Denmark Blavatnik School of Government. COVID-19 GOVERNMENT RESPONSE TRACKER Oxford A global panel database of pandemic policies (Oxford COVID-19 Government Response Tracker) Google COVID-19 Community Mobility Reports: Google All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted General practice during the corona epidemic -which patients can general practice fit and how?]: Praktiserende Laegers organisation & Dansk Selskab for Almen Medicin Brostrøm gives the green light to singles, sex is good sex is healthy.] Danmarks Radio: www.dr.dk Quarantine became the world's largest icebreaker on Tinder The last few months have been pretty severe"]: Berlingske Tidende COVID-19-related nationwide lockdown did not reduce the reported diagnoses of Chlamydia trachomatis and Neisseria gonorrhoeae in Finland Social distancing to combat COVID-19 led to a marked decrease in food-borne infections and sexually transmitted diseases in Spain Sexually transmitted infections during the COVID-19 outbreak: comparison of patients referring to the service of sexually transmitted diseases during the sanitary emergency with those referring during the common practice STIs and the COVID-19 pandemic: the lockdown does not stop sexual infections Reporting of sexually transmitted infections during the COVID-19 pandemic Modern romance The research was conducted using the resources of the Danish National Biobank, funded by the Novo Nordisk Foundation.All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted July 6, 2021. Supplementary