Effective public health measures to mitigate the spread of COVID-19: a systematic review

Background In December 2019, a novel coronavirus (2019-nCoV) was recognized in Wuhan, China. It was characterised by rapid spread causing a pandemic. Multiple public health interventions have been implemented worldwide to decrease the transmission of the 2019 novel coronavirus disease (COVID-19). The objective of this systematic review is to evaluate the implemented public health interventions to control the spread of the outbreak of COVID-19. Methods: We systematically searched PubMed, Science Direct and MedRxiv for relevant articles published in English up to March 16, 2021. We included quasi experimental studies, clinical trials, cohort studies, longitudinal studies, case-control studies and interrupted time series. We included the studies that investigated the effect of the implemented public health measures to prevent and control the outbreak of 2019 novel coronavirus disease (COVID-19). Results The database search using the predefined combinations of Mesh terms found 13,497 studies of which 3595 in PubMed, 7393 in Science Direct 2509 preprints in MedRxiv. After removal of the duplicates and the critical reading only 18 articles were included in this systematic review and processed for data extraction. Conclusions Public health interventions and non-pharmaceutical measurements were effective in decreasing the transmission of COVID-19. The included studies showed that travel restrictions, borders measures, quarantine of travellers arriving from affected countries, city lockdown, restrictions of mass gathering, isolation and quarantine of confirmed cases and close contacts, social distancing measures, compulsory mask wearing, contact tracing and testing, school closures and personal protective equipment use among health workers were effective in mitigating the spread of COVID-19.


Introduction
In the twenty-first century, two highly pathogenic human coronaviruses (HCoVs) severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) emerged from animal reservoirs to cause global epidemics. In December 2019, yet another pathogenic HCoV, 2019 novel coronavirus (2019-nCoV), was recognized in Wuhan, China, and has caused serious illness and death [1]. This novel coronavirus is characterised by rapid spread and high contagiousness [2] which caused a pandemic as it was spreading rapidly between and within the countries. As of 18 March 2021 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 121.8 million cases and 2.69 deaths [3] affecting 221 countries and territories. Since the beginning of the COVID-19 pandemic several public health interventions have been implemented worldwide to reduce the transmission of the SARS-CoV-2. In previous experiences, like the 1918-19 H1N1 influenza pandemic where no treatments or vaccines were available to treat or prevent the disease multiple non-pharmaceutical interventions were successful at reducing case numbers and have shown to be effective when implemented early in the epidemic. Those interventions include travel bans and restrictions, schools and workplace closures, isolating infected persons, quarantine of exposed persons, social distancing and cancellation of mass gathering events. Those interventions have shown to be effective ways to respond to the outbreak when implemented early in the epidemic [4][5][6][7][8][9]. However the effectiveness of those interventions whether applied alone or simultaneously still unclear and results from previous modelling studies are inconsistent [10].
Within this systematic review we aimed to evaluate the public health interventions and the nonpharmaceutical control measures that have been implemented worldwide to mitigate and control the spread of the outbreak of 2019 novel coronavirus disease .

Search strategy and selection criteria
We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [11]. The protocol of this systematic review was published on PROSPERO (registration number CRD42020196018). Given the nature of this research study no approval by an institutional review board was necessary. We systematically searched PubMed, Science Direct and MedRxiv for relevant articles published in English up to March 16, 2021  In Science Direct and MedRxiv we used the following terms: "Public Health measures" and "covid-19".

Study eligibility and quality assessment
We included articles published only in English language up to March 16, 2021, clinical trials, quasi experimental studies, cohort studies, longitudinal studies, case-control studies, and interrupted time series. The studies that investigated the effect of the non-pharmaceutical interventions such as social distancing, lockdown, quarantine, mobility and travel restrictions, border control measures, contact tracing, isolation of cases that have been implemented to mitigate, prevent and control the outbreak of 2019 novel coronavirus disease . We excluded articles published in a language other than English; narrative literature reviews, policy reviews, case studies, case reports, case series, cross-sectional studies, ecological studies, commentaries, editorials, letters, point of views, simulation studies, modelling studies, prediction studies, qualitative studies,systematic reviews and meta-analysis.
The database search was conducted by one author (AI) who did the tiles and abstracts screening in order to identify the eligible studies for full text review with referral to (MJ) and (DW). Both authors (AI, DW) did the full text review of the studies that potentially met eligibility criteria and checked their relevance with referral to a third author (MJ) in case of discordance. Any discrepancy between the reviewers was resolved by discussion.

Data analysis
Two authors (AI, DW) did the data extraction using a standardized form to collect the relevant data from each article. The form included study identification features (authors, article title, country of origin), study characteristics (aim of the study, study design), characteristics of the studied population, public health interventions that has been implemented (description of the intervention(s) and control(s) if applicable), outcomes and authors' conclusions. The included studies were evaluated for quality and risk of bias using the Effective Public Health Practice Project (EPHPP) quality assessment tool quantitative studies [12]. All studies were independently assessed for quality by two reviewers (AI, DW), with disagreements resolved by discussion until full consensus was reached with referral to (MJ) and (ZN). Level of evidence and grade of recommendation of the included studies were assessed according to the Scottish Intercollegiate Guidelines Network (SIGN) system [13].

Results
The database search in PubMed and Science Direct using the predefined combinations of Mesh terms found 13,497 studies of which 3595 in PubMed, 7393 in Science Direct 2509 preprints in MedRxiv. After removal of the duplicates 12,433 articles remained. During the screening stage one article was excluded as it was retracted and 12,139 records were excluded on basis of title and abstract. After the critical reading of the 293 remaining articles, 275 articles were excluded seeing that they didn't meet the eligibility criteria and only 18 articles were included in this systematic review and processed for data extraction. Fig. 1 summarized the described outcomes. The characteristics of the included studies and the main results were summarized Table 1 including the following items: authors, country, study design, objective, methods and main outcomes. For the quality assessment results the quality of 14 (77.77%) included studies [14-16, 19-21, 23-29, 31] was moderate, the quality of two studies [18,22] was strong and the quality was weak for the two remaining studies [17,30] ( Table 2). As for the results of the level of evidence and grade of recommendation assessment, six studies had low level of evidence and low grade of recommendation [16,17,19,21,24,30]. Ten studies had moderate level of evidence and low grade of recommendation [14,15,20,22,23,[25][26][27][28][29], one study had moderate level of evidence and moderate grade of recommendation [18] and only one study had high level of evidence and high grade of recommendation [31] (Table 3). Three studies [16,22,26] have found that travel entry restrictions and bans, borders control measures and quarantine of travellers especially the ones arriving from affected countries along with other interventions was effective in reducing the spread of COVID-19. Seven studies [14,15,23,24,27,30,31] have shown that city lockdown, stay at home orders, traffic suspension and restrictions of mass gathering are strongly associated with reduced growth rate of COVID-19 confirmed cases and reduction in the epidemic growth. Moreover in their study Salvatore M et al. [23] found that lockdown was partly effective due to state level variations which should be considered in      Singh BB et al [30], India (preprint)

Longitudinal study
Evaluation of the public health interventions using the effective reproduction number (Rt), in key lockdown periods in India.
Laboratory-confirmed COVID-19 infections rates per day and effective reproduction number (Rt) were estimated for 4 periods (Pre-lockdown and Lockdown Phases 1 to 3) according to nationally implemented phased interventions. Adoption of these measures was estimated using Google mobility data. Estimates at the national level and for 12 Indian states most affected by COVID-19 are presented. Using data are publicly available from Google a domain-specific mobility index was constructed using India's mobility report (Google Inc., Mountain View, CA, USA). domain-specific mobility index was constructed for the country and 12 Indian states.
Median mobility in India decreased in all contact domains, with the lowest being 21% in retail/recreation (95% CI 13-46%), except home which increased to 129% (95% CI 117-132%) compared to the 100% baseline value. The Indian government imposed strict contact mitigation, followed by a phased relaxation, which slowed the spread of COVID-19 epidemic progression in India.

Quasi experimental study
Analyse the unique casecontrolled epidemiological dataset arising from the selective lockdown of parts of Northern Denmark, but not others, as a consequence of the spread of mink-related mutations in November 2020.
A quasi-natural experiment in the Danish region of Northern Jutland. 7 of the 11 municipalities of the region went into extreme lockdown in early November after the discovery of mutations of Sars-CoV-2 while the four other municipalities retained the moderate restrictions of the remaining country. Incidentally, the infection numbers in the two groups were compared.
While infection levels decreased, they did so before lockdown was effective. Infection numbers decreased as well in other municipalities without mandates. Control of infection pockets possibly together with voluntary social behaviour was apparently effective before the mandate which explains why the infection decline occurred before and in both the mandated and non-mandated areas. The findings of this study suggest that efficient infection surveillance and voluntary compliance make full lockdowns unnecessary at least in some circumstances.   [14-16, 18, 25, 26] found that identification of cases with isolation, quarantine of close contacts adding to home quarantine have been effective in suppressing transmission of COVID-19. Social and physical distancing measures have been proven in eight of the included studies [14, 16, 17, 20-22, 28, 29] to decrease the transmission of COVID-19. Thu TPB et al. [20] showed in their study that the time of promulgating the social distancing measures partly influences the intervention outcomes, adding to that population densities, crowding and socioeconomic variables as it was suggested by Krishnamachari B et al [29] Three studies [ 14,19,26] showed that compulsory mask wearing and community wide masking may contribute to the control of COVID-19 when they are implemented with other non-pharmaceutical control measures. In addition to that three studies [16,18,19] demonstrated that testing in conjunction with active case finding and contact tracing especially when implemented with isolation of cases and close contacts and social distancing are effective in reducing the transmission of COVID-19 and particularly important in maintaining suppression. Two studies [ 16,17] suggested that school closures together with the restrictions of mass gathering and physical distancing measures may have an effect in reducing the transmission of SARS-COV-2.Pan A et al [ 14], found in their study conducted in Wuhan, China that the rate of cases among health workers was substantially higher than in the general population in the period with there is no strong public health interventions which indicated a high risk of nosocomial infections and which might be inadequate use of personal protective equipment and lower awareness. However after increasing awareness and wider use of personal protective equipment adding to hospital-level prevention and management in parallel with the implementation of strong public heath interventions the rate of confirmed cases quickly decreased and furthermore no new case were reported among local health workers which prove that protecting heath care workers is an important measure in controlling an outbreak of a high transmissible infectious disease. Finally Zeng K et al. [26] and Seong H et al. [21] suggested that early community mask wearing and timely border control interventions using modern digital tools in addition to early and timely measures with strengthened social distancing interventions should be implemented to suppress and control the COVID-19 pandemic effectively.

Discussion
We found that public health interventions and nonpharmaceutical control measures were effective in reducing the transmission of COVID-19 and were associated with reduced epidemic growth. The identified studies showed that travel restrictions, borders measures, quarantine of travellers arriving from affected countries, city lockdown, restrictions of mass gathering, isolation and quarantine of confirmed cases and close contacts, social distancing measures, compulsory mask wearing, contact tracing and testing, school closures and personal protective equipment use among health workers were effective in mitigating the spread of COVID-19 with varying degrees. Our results are in line with the findings of other studies [32][33][34] that demonstrated that public health measures and non-pharmaceutical control strategies are effective in mitigating the current pandemic of COVID-19 and in some countries aggressive and extreme interventions are probably needed to bring the epidemic under control and to prevent very large number of deaths and excess hospitals capacities. Travel and entry restrictions, borders measures and quarantine of travellers arriving from affected countries were effective in controlling the spread of infection caused by SARS-CoV 2. Those interventions have been shown to be effective as well in other studies [ 6,35], which suggest that travel restrictions and border control measures including surveillance targeting inbound travellers from affected countries and 14-day quarantine for arriving passengers adding to other public health interventions were associated with a stabilization of case numbers.
City lockdown, restriction of mass gathering physical distancing and stay at home policies has been shown to be effective as well in reducing the spread of SARS-CoV2 in the current study. Further studies support these findings and showed that lockdown measurements and stay at home orders were efficient in controlling and slowing down the spread of the epidemic [36][37][38][39] were strongly associated with the containment of COVID-19 [40]. A rapid review of modelling studies [ 41] found that quarantine is crucial in decreasing incidence and mortality in the pandemic of COVID-19. Moreover in order to ensure effectiveness it is very important implement quarantine measures especially in combination with other public health interventions at the early stage of the epidemic. Adding to that, in their study Marco Vinceti et al [ 42] showed the less rigid lockdown measurements led to an insufficient reduction in transmission to reverse the outbreak and with a tighter lockdown mobility and person to person transmission decreased enough to bring down transmission straight off below the level required to counteract spread of SARS-CoV-2 infection. In addition to that physical distancing strategies and restriction of human mobility [ 43,44] has been showed to have a notable effect on controlling the spread of the COVID-19 outbreak.
Isolation and quarantine measures of contacts and close contacts adding to contact tracing are crucial to control the outbreak of COVID-19 and reduce the human to human transmission. Those results are consistent with the findings of other studies [45][46][47][48] which indicate successful contact tracing and isolation of cases and close contacts are highly important to control the outbreak and to ensure a lower reproduction number below 1. These interventions might be more effective if combined with other measures such as physical distancing, self-isolation and testing. Testing is a key intervention in mitigating the spread of COVID-19 especially when it is applied in conjunction with tracing and isolation of cases and close contacts [49].
Compulsory mask wearing and community wide masking policies are essential in controlling the pandemic of COVID-19. Authors of a rapid systematic review [50] on the efficacy of face masks suggest that masking wearing could be beneficial in the context of COVID-19 outbreak especially universal community mask use and in the health care settings as well. Findings from a systematic review and meta-analysis [51] showed that mask wearing by health workers and non-health workers and in the general community is and efficient in preventing the infection by SARS-CoV2. Another study [52] showed that wearing masks in public is crucial as a preventive measure to ensure a significant reduction in the daily infected cases. In addition to that a prospective cohort study [53] found that the risk of infection by SARS-CoV-2 is increase among frontline health workers, therefore adequate strategies should be implemented to ensure the availability of personal protective equipments in order to protect health workers from COVID-19. Moreover timing is very important while implementing non-pharmaceutical interventions which should be initiated early when the numbers of COVID-19 cases are low as it was demonstrated in an observational study conducted by Qureshi A I et al [54] School closures had been found to be effective in reducing the transmission of COVID-19, recently this intervention has been widely discussed; some studies [55,56] found that school closures were associated with a reduction in the transmission of COVID-19 and in the mortality rate as well. However, other studies [57,58] showed that school closures don't have any mitigating impact on the transmission of COVID-19 as children are likely to be asymptomatic and they don't seem to be greater transmitters in comparison with adults.
Further studies [59,60] found additional tools that help prevent and control the COVID-19 pandemic such as internet hospitals and virtual care which presents a promising potential in the control of the COVID-19 outbreak as they are capable of reducing the emergency room visits, reducing the risk of nosocomial crossinfection by treating patients remotely, prevent the shortage of health care resources and promote personal prevention measures such as social distancing, mask wearing and hand hygiene. A systematic review [61] showed that telehealth is capable of minimizing the risk of COVID-19 transmission by decreasing the physical contacts adding to providing continuous community care.
This systematic review has several limitations, the included studies have heterogeneous methodology and most of them lack a control group and a vigorous study design. Although most of the included studies have moderate quality and for the remaining studies; two studies have low quality and only two studies have strong quality. Also, most of the included studies have moderate level of evidence and low grade of recommendation, six studies have low level of evidence and low grade of recommendation, only one study has moderate level of evidence and grade of recommendation and only one study as well has high level of evidence and grade of recommendation. In addition to that most of the public health interventions are implemented simultaneously or within a short period of time which means that it is difficult to evaluate the effect of each intervention alone accurately, consequently we can either underestimate or overestimate their impact on the COVID-19 pandemic. Future research studies which have rigorous methodology especially experimental and quasi experimental studies are needed to properly evaluate the outcomes of these public health interventions and nonpharmaceutical measures.

Conclusion
With no effective treatment and vaccine against SARS-CoV-2, public health measures and non-pharmaceutical interventions are vital to reduce the infection and mortality rate. Some interventions are not efficient enough when implemented alone and could not contain the outbreak, thus, depending on the country and the phase of the epidemic multiple interventions are needed to be applied together in order to bring the outbreak under control.