key: cord-0825086-gmwrrjvj authors: Masai, Abednego Nzyuko; Akin, Prof Levent title: Practice of COVID-19 preventive measures and risk of acute respiratory infections: a longitudinal study in students from 95 countries date: 2021-10-12 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.10.017 sha: 3775d04d7690908d14773a9d63c1029878dee62a doc_id: 825086 cord_uid: gmwrrjvj Objectives We aimed to investigate whether the implementation of personal protective measures against coronavirus disease 2019 reduced the transmission of influenza-like illnesses. Methods We followed 758 international students from 95 countries located in five continents from October 2020 to March 2021. Their frequency of wearing masks, social distancing, washing hands, and avoiding crowded places as well as their reported cases of influenza-like illnesses were examined. We used Kaplan-Meier analysis to compare the occurrence of symptoms of influenza-like illnesses among participants who adhered with those who did not adhere to the personal protective measures. Results From October 2020 to March 2021, 139 (18%) students reported symptoms of influenza-like illnesses. The survival analysis showed that students who frequently wore face masks, exercised physical distancing, and disinfected their hands had a reduced risk of influenza-like illnesses. We found a two-fold increased risk of influenza-like illnesses among participants who did not implement all the personal protective measures as compared with those who adhered to the measures (Hazard ratio=2.16, 95%CI=1.53-3.05, P<0.001). Conclusions Our findings suggest that personal protective measures with high feasibility and high acceptability could be implemented during influenza epidemics to reduce transmission. After the widespread implementation of measures to mitigate COVID-19 (coronavirus disease 2019), influenza activity and influenza-like illnesses declined sharply (Olsen et al., 2020) . The observed decline was attributed to artifactual changes related to hospital-seeking behaviors for respiratory illnesses and real changes related to a reduction in circulating respiratory viruses because of implementation of non-pharmaceutical interventions against COVID-19. Influenza data reported to the World Health Organization's FluNet platform in 2021 showed a continued decline in outpatient visits for influenza-like illnesses and confirmed influenzapositive results in most countries and regions in the Northern Hemisphere, Temperate zones, and Southern Hemisphere (WHO 2021a). The transmissibility of the SARS-CoV-2 (R0=2-6.1) (Ke et al, 2021) is higher than that of influenza (R0=1.28) (Biggerstaff et al., 2014) , which suggests that the coronavirus may have played a role in interrupting transmission of circulating influenza. The SARS-CoV-2, like other viruses that cause acute respiratory infections spread primarily by respiratory droplets. Thus, the practice of personal protective measures to protect against COVID-19 may have resulted in the decline in influenza-like illnesses during the 2020-2021 flu season. The World Health Organization recommended the following protective measures against COVID-19 transmission: Washing hands, keeping physical distance, avoiding touching eyes, nose and mouth, stay at home if you are sick, wearing masks, disinfecting frequently touched objects and surfaces, and avoiding the 3Cs (crowded places, close contacts, and closed spaces) (WHO 2021b) . There is evidence to support that wearing facemasks, protecting the eyes, and physical distancing (Chu et al, 2020) , and hand hygiene (Alzyood et al., 2020) can protect the transmission of SARS-CoV-2. However, data on the effectiveness of these measures in preventing community transmission of influenza-like illnesses is lacking (Olsen et al., 2020; Cowling et al., 2020) . We aimed to investigate the association between implementation of personal protective measures and cases of influenzalike illnesses in the general population by following a group of international students from 95 countries located in five continents during October 2020 to March 2021 period. We conducted a longitudinal observational study to assess cases of influenza-like illnesses among international students during the 2020-2021 flu season. Data collection commenced in October 2020 and concluded at the end of March 2021. Participants of this study comprised of international students enrolled in undergraduate or postgraduate programs in universities in Turkey. The respondents were required to be at least 18 years and above. The participants were identified from a database of international students on the Turkish Scholarship at the Presidency for Turks Abroad and Related Communities. We collected data through monthly online surveys, which were delivered to the participants through their students' information systems. We explained the purpose of the study and the confidentiality of responses to the students. The students gave informed consent before participating in the study. Potential participants were screened based on the responses given in the baseline questionnaire to determine whether they met the study's inclusion criteria. Participants enrolled answered questions about their frequency of implementing personal protective measures and if they experienced symptoms of ILI in the previous month. We assessed respondents' level of personal protective measures using five items recommended by the WHO, which included the frequency of wearing facemasks, physical distancing, hand hygiene, surface disinfection, and avoiding crowded places. Participants reported their frequency of implementing the measures using a 5-Likert scale. The scale reliability was examined because it had not been validated previously in the context of this research. Cronbach's alpha test was calculated for all participants. Results indicated that the scale had good reliability (α=0.81, 95% CI 0.79-0.83). The survey forms were also pretested on a convenience sample of 50 male and 50 female international students (n=100) outside the target group to ensure clarity of interpretation and improve the validity of responses. We assessed influenza-like illnesses by symptoms of an acute respiratory infection with an onset within 10 days, fever of greater than 38 degrees, and persistent cough in the absence of an alternative causative agent (Stellrecht 2016) . Students who reported symptoms of fever, sore throat, and persistent cough and did not receive any confirmatory tests were regarded as having symptoms of influenza-like illnesses, which was consistent with the World Health Organization's case definition of influenza-like illnesses. Ethical approval for this study was obtained from the Non-Interventional Clinical Research Ethics Committee of Hacettepe University (No. GO 20/885), and informed consent was given by all the participants. Moreover, approval for the study was obtained from Ministry of Health of the Republic of Turkey. We first grouped categorical variables with ordinal response scales, including the level of personal protective measures. We grouped responses to the frequency of wearing facemasks, washing hands, physical distancing, avoiding crowded places, and disinfecting surfaces into three groups as 2 (Frequently or Always), 1(Sometimes), and 0 (Never). All participants to some extent implemented some of the measures to protect themselves from coronavirus infection. The personal protective measures scores (0, 1 or 2) were added for each student to give the overall implementation of personal protective measures with 0 and 10 being the lowest an highest possible score, respectively. We compared frequency of practicing personal protective measures among students who had influenza-like illnesses with those who did not have influenza-like illnesses. We estimated the first occurrence of influenza-like illnesses over the 2020-2021 flu season using Kaplan-Meier analysis. Before conducting the survival analysis, the assumption of homogeneity of variances was tested and satisfied based on Levene's F-test (F=1.43, p=0.49). We compared the six-month survival of the students who implemented all the personal protective measures with those who did not implement measures, with the event of interest determined as experiencing symptoms of influenza-like illnesses or censoring. We used long rank test to compare and understand the differences between the survival distributions. Using a multivariate Cox regression (Proportional hazards) analysis, we examined the association between students' level of implementing personal protective measures against COVID-19 and occurrence of influenza-like illnesses, factoring the time of observation or censoring. The first regression analysis included covariates such as gender, age, country of origin, and current smoking status in addition to the implementation of the personal protective measures. The initial results showed that gender (p=0.71), age (p=0.59), country of origin (p=0.65), and smoking (p=0.26) did not significantly affect the symptoms of influenza-like illnesses. Therefore, the covariates were removed from the regression model, and the analysis was rerun only with the six personal protective measures against COVID-19 (wearing facemasks, hand hygiene, physical distancing, surface disinfection, and avoiding crowded places) set as the covariates. All statistical analyses were done with R version 4.3.3. Of the total students who received the survey (n=1000), 847 students agreed to participate and took part in the baseline survey (Response rate 84.7%). 79 students were excluded from the study because they were not enrolled in universities in Turkey at the time of the study. An additional 10 students were excluded from the study because they reported being permanent residents in Turkey, thus, did not meet the classification of an international student. Therefore, we sent monthly follow-up surveys to 758 students who met the inclusion criteria (Table 1) at the beginning of every month, from November 2020 to March 2021, and a reminder in the middle of every month to maximize the response rate. A total of 139 (18%) international students reported symptoms of acute respiratory infections between October 2020 and March 2021 ( Figure 2 ). Table 2 shows the implementation of personal protective measures by the students. We found that participants who did not have influenza-like illnesses reported higher implementation of all the personal protective measures compared to participants who experienced the symptoms. We observed that the level of personal protection against COVID-19 was higher among students who did not have influenza-like illnesses ( Figure 3 ) further indicating that there was a link between implementation of the measures against coronavirus and cases of influenza-like illnesses. Of the students who had influenza-like illnesses, 62.6% (n=87) had scores below the median and 37.4% (n=52) had scores above the median person protective measure. Results of the survival analysis showed that the overall probability of being event-free among students with personal protective measure scores above the median was higher than students who had scores below the median (Figure 4 ). There was a significant difference in survival distribution between participants who scored below the median and those who score above the median, log-rank χ2=23, p<0.001. The results from the Kaplan Meier method showed that international students who adhered to implementing the personal protective measures had a reduced risk of acquiring respiratory infections. Having identified that students' implementation of personal protective measures played a role in the observed decline in the cases of influenza-like illnesses, we conducted a Cox proportional hazard regression analysis to determine the measure that offered the highest protection to international students. The regression analysis showed that at a given point in time, students who wore facemasks were 33.6% less likely to show symptoms of influenzalike illnesses than students who did not wear facemask adjusting for all the other personal protective measures (Hazard Ratio=0.664, p=0.006) . Similarly, students who exercised physical distancing measures were 23.5% less likely to report symptoms of influenza-like illnesses when compared to those who did not adhere to social distancing adjusting for the other measures (Hazard ratio= 0.765, 95%CI=0.610 -0.960, p=0.020). Furthermore, international students who frequently disinfected their hands were 17.1 % less likely to report symptoms of influenza-like illnesses than those who did not frequently disinfect their hands (Hazard ratio=0.821, 95%CI=0.793 -0.915, p=0.029). We found a two-fold increased risk of influenza-like illnesses among students who did not implement all the personal protective measures as compared with those who adhered to the measures (HR=2.16, 95%CI=1.53-3.05, P<0.001). There was no significant association between surface disinfection (p=0.298) and avoiding crowded places (p=0.730) with the reported symptoms of influenza-like illnesses among the participants. PPMS was calculated from students' frequency of wearing facemasks, physical distancing, hand hygiene, surface disinfection, and avoiding crowded places. We assigned scores of 2, 1, and 0 to students who always/frequently, sometimes, and never implemented a specific measure. We then calculated the PPMS by adding the sum of the scores for each of the five measures. The highest score PPMS was 10 and the lowest score was 0. Regarding the implementation of facemasks, results of the Cox proportional hazard regression analysis showed that students who wore facemasks were 33.6% less likely to show symptoms of influenza-like illnesses compared to students who did not wear facemask adjusting for all the other personal protective measures (Hazard Ratio=0.664, p=0.006) . The current study did not distinguish between cloth, surgical, and N95 masks. Thus, study results showed the effectiveness of wearing masks in general among the international students' population. Previous studies have shown that facemasks are effective in preventing the transmission of respiratory infections (Leung et al., 2020) . The present study investigated the impact of personal protective measures in influenza-like illnesses by observing a group of international students from 95 countries over a period of six months. Additionally, the compliance rate of mask-wearing among international students in the present study was high (97.87%). Therefore, the results of this study provide a reliable estimate of the impact of wearing masks in preventing acute respiratory infections among students, in the context where facemasks are widely adopted. We also identified an association between students' practice of physical distancing measures and cases of influenza-like illnesses. The percentage of students with symptoms of ILIs who always or frequently implemented physical distancing measures was significantly lower when compared to students without symptoms of ILIs (p<0.001). Furthermore, students who adhered to physical distancing measures were 23.5% less likely to report symptoms of influenza-like illnesses when compared to those who did not adhere to physical distancing adjusting for the other measures (Hazard ratio= 0.765, 95%CI=0.610 -0.960, p=0.020). The study finding is consistent with findings from previous studies, which have shown that physical distancing measures are effective in interrupting the transmission of respiratory viruses (Chu et al., 2020; Poole et al., 2020) . One study showed that influenza transmissibility declined by 44% after the implementation of physical distancing measures and changes in population behavior (Cowling et al., 2020) . Previous studies have shown that hand hygiene reduces respiratory infections by 16-21% (Aiello et al., 2008) . Results from the present study also showed a significant association between the frequency of handwashing/disinfection and reported cases of influenza-like illnesses among international students. In particular, students who frequently disinfected their hands were 17.1 % less likely to report symptoms of influenza-like illnesses than those who did not frequently disinfect their hands (Hazard ratio=0.821, 95%CI=0.793 -0.915, p=0.029). Since the compliance rate among study participants was high with 91.56% (n=694) of the students reporting always or frequently disinfecting their hands, the results of this study provide a reliable estimate of the impact of hand hygiene in preventing influenza-like in the context of a pandemic. We did not find any significant association between cases of influenza-like illnesses and avoiding crowded places. There is evidence on benefits of reducing social mixing (Prem et al., 2020) . However, the evidence on direct impact of avoiding crowded places in preventing respiratory virus infection in individuals remains scarce. Additionally, study findings did not show a significant association between surface disinfection and reported cases of influenzalike illnesses among international students. This non-significant finding may be due to the study setting and the target population. One study showed that surface disinfection was effective in reducing secondary transmission of COVID-19 transmission in households (Wang et al., 2020) . In the present study, we observed the international students' practice of personal COVID-19 measures in the community. Overall, adherence to the five personal protective measures recommended by the World Health Organization prevented cases of influenza-like illnesses among international students enrolled in this study. We found that participants who did not implement all the measures were two times more likely to have influenza-like illnesses compared to students who frequently implemented all the measures (Hazard Ratio=2.16, ). This showed that the personal protective measures worked synergistically and the implementation of all measures offered higher protection to international students compared to single measures. Our study has some limitations. First, Participants in the study gave a self-reported evaluation of their implementation status of personal protective measures against COVID-19, which may have led to a possible overestimation of their implementation status. To resolve any potential social desirability bias, we used anonymous online surveys and we assured the confidentiality of their responses at the introductory part of every survey. Second, the study evaluated the preventive effects of five personal protective measures. Other measures may have contributed to suppressing transmission of respiratory infections. Third, the study was conducted on students and this limits the generalizability of the findings to the general population. Despite these limitations, to the best of our knowledge, this is the first study to explore the practice of personal protection measures and the risk of influenza-like illnesses during the 2020-2021 flu season. In conclusion, our study found that personal measures to protect against COVID-19 (including wearing facemasks, hand hygiene, and social distancing) prevented the transmission of acute respiratory infections during the 2020-2021 flu season. Our findings suggest that personal protective measures with high feasibility and high acceptability could be implemented during influenza epidemics to reduce transmission, particularly in populations at the highest risk of developing severe complications. Therefore, future studies can investigate the utility of these measures in people who are at risk of severe complications. ANM designed the study, collected and analyzed the data, prepared, and revised the manuscript. LA designed and supervised the study, analyzed the data, and revised the manuscript. All authors declare no competing interests. The datasets supporting the conclusions of this article are available from the corresponding author, and can be shared upon request. Chi square (with Fisher's exact test) was use to compare implementation of personal protective measures between participants who had influenza-like illnesses and those who did not have influenza-like illnesses. There was a significant difference in the use of facemask (p=0.006), physical distancing (p<0.001), hand hygiene (p=0.004), surface disinfection (p=0.0002), and avoiding crowded places (p<0.001). Effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis COVID-19 reinforces the importance of handwashing Estimates of the reproduction number for seasonal, pandemic, and zoonotic influenza: a systematic review of the literature COVID-19 Systematic Urgent Review Group Effort (SURGE) study authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis Impact assessment of nonpharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study. Lancet Public Health Chapter 11 -Molecular Testing for Respiratory Viruses, Editor(s): William B Diagnostic Molecular Pathology Estimating the reproductive number R0 of SARS-CoV-2 in the United States and eight European countries and implications for vaccination Author Correction: Respiratory virus shedding in exhaled breath and efficacy of face masks Healthcare services utilization among international students in Ankara, Turkey: a cross-sectional study Decreased Influenza Activity During the COVID-19 Pandemic -United States Physical distancing in schools for SARS-CoV-2 and the resurgence of rhinovirus The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study Emerg Infect Dis Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China World Health Organization. Coronavirus disease (COVID-19) advice to the public The authors wish to thank all international students who gave their time to participate in the study.Funding We did not receive any funding for this research.