COVID | Free Full-Text | A Comparative Analysis of COVID-19 Response Measures and Their Impact on Mortality Rate

The coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, leading to physical disabilities and countless deaths [1,2,3,4,5,6]. Countries implemented various measures against it; measures taken globally by 2022 are reported here [7]. By 2023, many countries had ceased these measures, but until then, they had adopted a range of strategies, including societal enforcements such as lockdowns, movement restrictions, office closures, quarantines, and individual precautions like maintaining distance and wearing masks. The World Health Organization (WHO) and the European Centre for Disease Prevention and Control recommend vaccines first, followed by non-medical measures that can be taken locally and individually [8,9].

Studies examining the actual effects of such measures require accurate measurements and proper analyses [10]. In the case of people’s movement, stringent measures such as lockdowns effectively restricted people’s movement, whereas recommendations for restraint such as mild physical distancing were observed to reduce traffic [11]. In Japan, the government urged people to avoid nighttime outings and travel. This led to a considerable reduction in people’s movements; however, the number of patients and deaths did not significantly change [12]. Although there is a mild request for self-restraint, maintaining distance can be challenging for vulnerable population groups [13].

There were significant differences in isolation measures from country to country [14], and their effectiveness varied. Lockdowns and shelter-in-place orders in Europe and the United States have done little to reduce mortality rates, although they involve strong enforcement [15]. Some countries, such as Iceland and Taiwan, successfully contained the virus by conducting frequent polymerase chain reaction (PCR) tests and quickly identifying new cases [16,17,18]. Others have attempted lockdown areas to contain the spread of the virus. However, the effectiveness of these measures varies significantly, with many countries experiencing delayed epidemic detection and inefficient disease control. The effectiveness of frequent PCR testing and strict lockdown has been demonstrated in China, Australia, and New Zealand [12,19]. However, with the emergence of a more infectious Omicron variant, strict lockdowns have become inadequate. At that time, residents began to protest against the lockdowns, and the governments terminated the lockdown policy without any consideration for a soft landing [20,21,22]. Many other countries, such as Japan, have not conducted sufficient PCR tests, making it difficult to understand the trends in infection [12]. In some countries, such as Sweden, lockdowns were not implemented, and the public was left to make their own decisions [23]. In these countries, the epidemic progressed despite residents’ self-help efforts. Thus, comparing the differences in the effects of these measures is crucial. The results of a 2022 study on the impact of various measures in European countries with the highest patient numbers are summarised as follows [24]. This is compared with 2021; during this period, the more virulent Omicron variant was prevalent, worsening the situation. Social responses such as cancelling gatherings and shutting down transport companies proved effective and were inversely correlated with infection numbers. The effectiveness of these measures has been recognised since the epidemic’s onset [25]. Enhanced surveillance is commonplace in all regions where it has shown efficacy. Furthermore, a German study indicated that combined general behavioural changes were the most effective non-pharmaceutical intervention [26].

The views about the effectiveness of the vaccine vary; specifically, some studies suggest that the vaccine reduces both deaths and infections by 50–80% [27,28], while others suggest that there is no significant difference [29]. Nevertheless, there is a consensus that the vaccine is less effective against the Omicron variant. Supporting this, sequence analysis suggests that the Omicron variant has escaped immunity from a previous vaccine [30]. Both the numbers of vaccinations and boosters were strongly and positively correlated with the number of infections [24]. These results suggest that the vaccine is ineffective, at least against the omicron variant, and that vaccination may increase the number of infections. Furthermore, there has been concern that repeated vaccinations might lead to a decrease in immunity [31,32]; this has been confirmed to manifest as an increase in immunoglobulin (Ig) G4 [33,34,35].

Technical difficulties in identifying trends in the patient population, which can increase or decrease rapidly, may account for the failure to detect epidemics. Thus, adaptation to the susceptible–infected–recovered (SIR) model proves challenging, and it targeted a relatively limited number of individuals; the period of logarithmic increase was brief, rendering the estimation of R₀ [36] less pertinent, as viruses not initially human gradually acclimatised to humans. Those that become more infectious repeatedly penetrate defence systems and cause epidemics [37,38]. When switching hosts, the mutation rate is particularly rapid, and infectivity becomes stronger [39]. Therefore, the most recent Omicron variant, which has persisted for more than one year, is highly infectious [40]. Moreover, the basic reproduction number R₀, which the SIR model originally emphasised, has a lognormal distribution, is mathematically unstable, and requires complicated calculations for a precise estimation [36]. This makes it difficult to use as an indicator of trend. Therefore, it is more realistic to work with a logarithmic growth rate, K, which has a base value of two. This number represents the rate of change in the number of patients N(t) at t and is expressed as N(t) = N₀2^Kt. More information has been published in previous studies [36] and can be found in Appendix A. This is easy to calculate and suitable as an indicator of the epidemic phase. The changes in K are shown in the following data.

Strict policies, such as the stern lockdowns implemented in China, Australia, and New Zealand, proved to be unsuitable for controlling the pandemic, which is a battle expected to be protracted (Figure 4E and Figure S2A,L). Moreover, a soft landing strategy is necessary to gradually phase out these stringent measures [20]. The isolation of infected people can be achieved via lockdowns; however, this places a heavy burden on the population, and it should be noted that Iceland did not opt for this [17]. Naturally, many citizens opposed the lockdown, which put pressure on politicians [73]. Eventually, the leaders of these countries, who had well-controlled epidemics via strict lockdowns, withdrew their zero-COVID policies [19,21,22]. However, this led to an epidemic (Figure 4E and Figure S2A,L); it is likely that people accustomed to the lockdown had no means of self-defence. A few countries have stopped tracking the number of affected patients [1]. In contrast, Sweden continues this practice, enabling inspection of the mortality rate (Figure 3D). However, other disheartened governments may forsake necessary actions. This represents an additional drawback of lockdowns. The perceived success in controlling infection could result in overlooking the critical establishment of patient detection methods. This renders early treatment unfeasible and impairs infection control post-lockdown. Pertaining to other countries, lockdowns in Europe and the US have not been successful [15]; similarly, all measures in Japan failed (Figure 3, Figure 4, Figures S1 and S2) [12]. Another reason why countries that took more moderate measures did not succeed is probably due to the fact that they started too late. The peak of K, which showed an exponential increase, occurred several weeks earlier than the peak of infected individuals (Figure 3 and Figure S1, Appendix A). By the time politicians began to take action, the infection was already on the verge of convergence, regardless of whether they had taken action. For this reason, observations should be made using an easily calculable indicator such as K.

mRNA vaccines, an entirely new technology [74], effectively prevented older variants (Figure 3F) [12,75]. However, it was ineffective against the newer Omicron variant (Figure 1B), which has undergone the selection pressure of vaccines and is in vogue. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underwent significant mutations during the pandemic [30]. Therefore, the mRNA vaccine, which initially showed great promise, is no longer effective in containing the pandemic and is unlikely to effectively reduce disease severity. Vaccine designs cannot keep pace with this mutation. Altering the mRNA sequence was required [76]. In a molecular biology sense, it was supposed to be a simple operation [74], but it took much longer than expected, and the new antigens were not effective. This task likely describes challenging problems known only to the individual concerned. The difficulty in continuously altering vaccine designs to accommodate viral changes. Consequently, mRNA vaccines may only be viable for a limited duration, necessitating the formulation of varied policies.

mRNA vaccines are expected to reduce the severity of illness and mortality; however, this remains largely unrealised (Figure 1 and Figure 4) [46,75,77,78]. The reduction in mortality rates was probably due to the low lethality of the early omicron variant [46] and not due to the vaccines (Figure 1C). In some countries, mRNA vaccines up to the Delta variant might have been able to reduce mortality (Figure 5). However, this effect was much weaker for the Omicron variant, and I wanted to obtain additional data to confirm this finding. Especially in the USA, the situation is somewhat unique; there is a difference in access to healthcare between those who received free and easily available vaccines and those who did not. The latter must include many anti-vaccine people [79] who do not trust modern healthcare systems. Delayed medical intervention for infections with highly virulent delta variants would increase mortality. This readily presumed difference confounds the epidemiological estimates. Therefore, these results [80] should not be accepted as they are presented. Indeed, at least on a global scale, the delta variant was in epidemic proportions when vaccination coverage reached 100%, but mortality was only marginally reduced at this stage (Figure 1C and Figure S2U). In Japan, the mortality rate persisted at a high level during the delta variant epidemic, a period when the vaccine’s preventative effect was most pronounced (Figure 5A). Those infected during this phase were predominantly unvaccinated individuals. Regardless of whether there was a decrease in mortality rates at that time, this phenomenon might have instilled in the medical community a misconception that the unvaccinated are at a higher risk of developing serious illnesses.

Reducing the number of anti-vax [81] people is a task for governments. Public trust in the government diminishes each time counterproductive measures are implemented, potentially leading to escalating distrust in healthcare and a probable rise in the number of anti-vaccination individuals. This scenario was previously witnessed in Japan. A panel of experts tasked with advising the government (although their recommendations are often overlooked) advocated for avoiding densely populated areas and wearing masks; nonetheless, anti-vaccination groups resist these suggestions. They assert their autonomy in decision making, disregarding expert advice on lifestyle choices. Regrettably, if such individuals contract the virus, they spread it and risk fatal outcomes if intervention occurs too late. To prevent an increase in such attitudes, it is crucial to engage in direct information dissemination and education, ensuring they are not overwhelmed. Legal backing is essential for enforcing mandatory quarantine of infected persons. However, isolating patients without proper medical care is unfeasible. Furthermore, persisting in endorsing vaccines of questionable efficacy can erode public confidence.

Paradoxically, due to the anti-vaccine sentiment surrounding vaccines, their efficacy might be unjustly overestimated. Initially, epidemiological comparisons between unvaccinated and vaccinated individuals pose challenges owing to confounding factors stemming from disparities in healthcare access. Alternatively, such comparisons could yield statistically significant differences. Nonetheless, it is pertinent to recognise that this might result from the amplification effect of a large sample size (n); being statistically significant and exhibiting a large effect size are distinct concepts. Had there been a substantial effect, a decrease in mortality rates would have been evident. Yet, this was not the case (Figure 1B,C and Figure 4).

It is unnatural and questionable why governments have not been proactive in publishing data on mortality and vaccination despite their importance to public health. If vaccines actually reduced mortality, the greatest publicity for vaccination would have come from these data. In Japan, despite aggressive promotion by the government [82], there is now a surplus of discarded mRNA vaccines [83]. Should the impact of the decrease in mortality already have dissipated, this would pose a challenge for the government, which has been called upon to account for the substantial unexplained budgets [82,83,84,85]. Vaccines have lost their efficacy in preventing epidemics (Figure 1B). If vaccines do not reduce mortality then there are no benefits but only risks [86,87,88] in current vaccinations.

It is believed that the efficacy of the vaccine wanes over time but can be restored by boosters [76]. This was true, at least in terms of the in vitro [30]. However, this simple and naïve view was regarded as apprehensive [31,32], and it is unclear whether in vitro titres are linked to the actual immune function. Furthermore, it was finally shown that repeated doses of mRNA vaccine can lead to a class change in antibodies to IgG4 [33,34,35]. This leads to a progressive decline in immunity. Therefore, an overreliance on mRNA vaccines for protection is essentially impractical. The vaccine failed to prevent the infection (Figure 1A). Furthermore, they did not diminish mortality rates (Figure 1B, Figure 4, Figure 5, and Figure S3). Vaccines that fail to prevent infection may not confer immunity; which mechanisms operate to enable vaccines to prevent severe diseases?

As can be observed that the Omicron variant led to a significantly higher number of cases compared to previous variants (Figure 1A), it is important to note that variants can mutate and enhance their infectivity, even during prolonged pandemics. This diminished the efficacy of initial measures such as social distancing, mask-wearing, vaccination, and lockdowns. The initial SARS-CoV-2 strain identified in this epidemic was not a human-specific virus; instead, it might have been a bat virus that, having been sustained in Vero cells, became infectious to primates. During human-to-human infections, the virus rapidly mutates to acclimate to humans in several directions [37,38], one of which is Omicron [40], the variant with the highest infectivity. This variant led to a reduction in the mortality rate; however, this was coincidental, as the virus was initially asymptomatic in many individuals. Consequently, weakening the virus does not undergo selective pressure. We should not invariably rely on such fortuitous outcomes. For instance, if the subsequent pandemic were to be influenza H5N1, it might manifest as a mutant capable of infecting mammals, transmitting via an intermediate host such as a pig, and subsequently infecting humans [89]. In this case, the virus changes rapidly in humans [39], altering its epitope and increasing its infectivity. However, if we can converge in the initial stage, we can avoid a pandemic before it occurs. This is the only stage at which a lockdown should be implemented. Therefore, a system that can quickly identify and alert the public to new infectious diseases is required.

The epidemic has subsided in some countries (Figure 3 and Figure S3). SARS-CoV2 has several conserved open reading frames (ORF) [37,40], which is a major difference from influenza, where all ORFs mutate at equal rates [71]. Presumably, SARS-CoV2 cannot repeat reinfection, such as influenza, for decades. As people become less immune, multivalent vaccines, especially those that can be used in developing countries, are required [39,40].

Data on daily changes in confirmed cases are important for fully ending the epidemic. As the number of infected individuals declined, several countries stopped reporting daily data [1]. For instance, in the USA, data are reported solely on a weekly basis, whereas in Australia and New Zealand, the frequency has become increasingly irregular. This poses a significant public health challenge, as accurate estimation of K is unattainable without consistent data. This situation leads to a rapid escalation and to an unobserved reduction, which is essential to sustain a decreasing trend. Per the SIR model, the patient count diminishes exponentially [36]. However, this phenomenon was not observed in these countries. Although the numbers are declining, small epidemics still recur, resulting in patient numbers ranging from tens to several thousands (Figure 3B,C and Figure S1A,L). The exponential decrease is initially rapid but progressively slows down. Achieving complete convergence is challenging if the government cannot sustain its motivation to keep the K low. While the development of effective vaccines and certain drugs is desirable, the government should not rely solely on them but prioritise immediate necessary actions. The only way to resolve this issue is via the continued identification and isolation of patients, a responsibility that should lie with the government.

The inability to contain the causes of problems stems from the fact that the remaining patients comprised a larger proportion of vulnerable individuals. These may include persons with underlying diseases who have diligently avoided infection and those who, failing to acquire immunity, become infected repeatedly. This scenario was likely in individuals who had received multiple vaccinations [33,34,35]. Therefore, these patients were more likely to be critically ill [90]. This disease can cause systemic symptoms [91] and long-lasting sequelae [2,3,4,5,92] in over 10% of individuals, and this rate is expected to worsen in the future as the number of susceptible individuals rises. The UK, Sweden, and Denmark may not have enough patients to cause a medical collapse now; however, their mortality rates have remained high, at approximately 2% (Figure 4E,F and Figure S2S). Even in the USA, where there may be a wider choice of medical care, the mortality rate is 1% (Table S1), which is quite high compared to the global data (Figure 1B).

The only viable method to protect vulnerable individuals is to bring the COVID-19 epidemic to a complete halt. Furthermore, the emergence of new strains is likely if outbreaks persist in these countries. Should these mutate significantly, they might precipitate another pandemic akin to the pdm09 strain of influenza that has engulfed the world [71]. Once the outbreak appears to have subsided, as observed in India, a new variant may commence circulation anew (Figure S1G). The continuation of measures and the detection of infected persons is imperative. The absence of such measures has led to a lack of convergence in Japan, with the number of infected individuals remaining unchanged, even between epidemic peaks (Figure 3F).

Numerous countries have underestimated the scale of the COVID-19 pandemic, although to differing extents (Tables S1 and S2). This underestimation likely stems from delayed detections, indicative of a shortfall in testing and isolation strategies. While the survey approached random sampling, a key limitation was the unknown sample size. Consequently, the precise number of patients and fatalities remains uncertain. In most African nations, there is a lack of investigation or response to infection cases; thus, the reported case numbers from Africa are markedly low (Table S1) [1]. This can only be estimated using certain methods. One promising method is to estimate excess deaths [6,67,68,69]. However, this estimation is contested; there is no substantiated evidence to confirm that the deceased were COVID-19 patients. For instance, an individual succumbing to a stroke may have perished due to the lack of prompt medical care. Nonetheless, it is probable that during normal circumstances, such an individual would have been rescued, thereby categorising their demise as a consequence of the COVID-19 pandemic.

Furthermore, epidemics can emerge in countries where minimal cases have been reported due to the absence of preventative measures and the evolving nature of variants during the epidemic’s course. Data collated by GISAID reveal a pronounced bias in the geographic origins of these data; for instance, most African nations, with the exception of South Africa, have not contributed sequences. Scant records exist for the early Omicron variants or their precursors; it is speculated that the Omicron variant originated within the African continent, yet it remains unsequenced there [40]. From a humanitarian perspective, and in order to prevent pandemics, effective infection control measures are essential in these countries. A need exists for an international organisation or collaborative effort focused on sequencing and patient detection. Specifically, the development of a vaccine that can be independently administered in these countries, such as an attenuated virus vaccine, is highly desirable. Importantly, this vaccine should not compromise immunity, even after repeated inoculations.

The consequences are significantly more severe if there is an absence of leadership that pays adequate attention to public health or, at the least, heeds expert opinion (Tables S1 and S2) [54,55,65]. This escalation is independent of the country’s guiding principles. A mechanism should exist whereby the scientific community can provide effective advice to the government. However, this system is not operating effectively in Japan. In January 2023, Japan reported over 10,000 deaths, a number anticipated to multiply substantially [6,64]. Nevertheless, the government has made a cabinet decision to exempt COVID-19 patients from quarantine and is campaigning for people to stop wearing masks [93,94,95]. In addition to limiting the number of PCR tests, the government abandoned counting cases, stating that it would announce the number of deaths after two months [96], thus hiding issues from the people. Additionally, they are still promoting mRNA vaccination [82]. How unscientific these policies are is beyond dispute [33,34,35,86,87,88,97,98,99]; these unscientific policies will definitely affect many patients, including vulnerable ones. Clearly, the government was reluctant to assume responsibility for public health. One of the essential roles of experts is to scrutinise policies and persuade voters to avoid electing unsuitable leaders. In a country with a democratic system for electing leaders, voters must consider these crisis responses: Will the candidates enforce forced hardship, remain ineffective, or ensure intelligent identification and quarantine of infected individuals? An expert can discern these differences. The prompt removal of unscientific politicians is a necessary step for effective public health management.

Although reports of confirmed cases are decreasing as many countries have stopped taking action [1], COVID-19 does not appear to have been completely terminated, and new variants continue to emerge [9,30]. Moreover, this will not be the last plague; similar pandemic diseases are likely to emerge in the future, and it remains to be determined whether it is more effective to respond with detection and quarantine as described herein or if alternative methods should be considered on a case-by-case basis. Consequently, objective and accurate measurements and analyses are essential [10].