Highlights
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• Lack of consensus on the end of the pandemic continues to occur.
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• There appears to be a tendency towards an endemic situation for COVID-19.
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• Long COVID may represent an important burden, which has also been the subject of controversies in the literature.
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• Combating scientific misinformation and maintaining continuous surveillance programs should be essential in this context.
On May 5, 2023, the World Health Organization (WHO) declared the end of the public health emergency of international concern (PHEIC) related to coronavirus disease 2019 (COVID-19),1 which has led to the discontinuation of many of the preventive measures against the disease around the world. This statement, in turn, has been the subject of important discussion and controversy both on the part of news vehicles and among scientists and specialists in the field. Many of these discussions have been based on epidemiological definitions by WHO and robust epidemiological data suggesting that the COVID-19 pandemic may not necessarily have come to the end.Reference Kupferschmidt and Wadman2 In addition, a possible pandemic of misinformation related especially to the negative effects of vaccination Reference Karafillakis, Van Damme and Hendrickx3 may also be impacting the epidemiological scientific field, along with other examples of scientific misinformation addressing, among other inconsistencies, the end to the COVID-19 pandemic even before the declaration of the end of the PHEIC situation.Reference Tovani-Palone4
Within this perspective it is important to note that “PHEIC” and “pandemic” correspond to 2 distinct concepts. According to The International Health Regulations “PHEIC” is “an extraordinary event which is determined to constitute a public health risk to other States through the international spread of disease and to potentially require a coordinated international response”.5 On the other hand, WHO defines “pandemic” as “the global spread of a pathogen or variant that infects human populations with limited or no immunity through sustained and high transmissibility from person to person, overwhelming health systems with severe morbidity and high mortality, and causing social and economic disruptions, all of which require effective national and global collaboration and coordination for its control”.6
Therefore, in the case of the COVID-19 pandemic, both a PHEIC and a pandemic have been experienced.5, 6 Although no longer considered a PHEIC by WHO, COVID-19 may still be a threat to global health because the pandemic characteristics remain uncertain.6, 7 If, on one hand, mass vaccination has apparently brought the situation under control, on the other hand, cases of the disease, hospitalizations, and deaths continue to be registered all over the world.7 Moreover, the lack of consensus among scientists, governments, and stakeholders on the current situationReference Kupferschmidt and Wadman2 may be contributing to further delaying its improvement, whether through the continued dissemination of scientific misinformation,Reference Tovani-Palone4 or even opposition to the implementation and/or revocation of appropriate public health measures. Considering this, here we discuss important aspects about the epidemiological situation of COVID-19, intriguing points about long COVID and its controversies, issues on scientific misinformation, tendencies in health surveillance, and other related recommendations.
Methods
To describe the most recent context of the global situation of the COVID-19 pandemic, analyses of data retrieved from the WHO coronavirus (COVID-19) dashboard7 were performed. In the first descriptive-comparative analysis, the period corresponding to the epidemiological weeks within the months of January to April of the years 2022 and 2023 were considered. The 2 following variables - number of confirmed cases and average number of tests for thousand - were measured through the sum of absolute values and by calculating the averages of the 2 periods, respectively. To estimate the possible number of cases expected for the year 2023, the product of the number of cases in 2022 and 1 minus the percentage decrease in the number of tests for thousand for the 2 periods considered was obtained.
For the second strategy of descriptive-comparative analysis, data relating to the epidemiological weeks within the years 2022 and 2023 and from January to September 2024 were included. To this end, the total number of confirmed COVID-19 cases was first systematically summed based on the years/months considered, grouping the sums of the total cases for each 4 consecutive epidemiological weeks. After that, the difference in the percentage variation in the number of confirmed COVID-19 cases was counted between each group of 4 consecutive epidemiological weeks and the previous group for each region over the period of respective months and/or years considered.
In all cases, data were calculated for each WHO region. Microsoft Excel version 16.74 was used to create the Table 1 and Figures 1 and 2 and perform the calculations mentioned. Data extraction for the first strategy of comparative analysis was carried out during the month of July 2023, while for the second strategy during the months of October and November 2024.
World situation of COVID-19, first 4 months of 2022 and 2023
* Obtained by multiplying the number of cases in 2022 by 1 minus the percentage decrease in the average tests per thousand.
COVID-19: Coronavirus disease 2019.
Source: Adapted from WHO.7
World COVID-19 cases from January 2022 to September 2024.
Nº of cases (in thousands and/or millions).
Nº of the week group: Each group corresponds to the total number of cases in 4 consecutive epidemiological weeks, with the exception of group 36.
COVID-19: Coronavirus disease 2019; AFR: African region; AMR: Americas region; EMR: Eastern Mediterranean region;
EUR: European region; SEAR: South-East Asia region; WPR: Western Pacific region.
Complete data for the Eastern Mediterranean region were available only up to the eighteenth epidemiological week for the year 2024 (during the data extraction period). Source: Data from WHO7 (Appendix 1 - supplementary material).
Percentage of change in the number of COVID-19 cases over time, January 2022-September 2024.
Nº of cases (% based on changes in thousands and/or millions).
Nº of the week group: Each group corresponds to the total number of cases in 4 consecutive epidemiological weeks, with the exception of group 36.
COVID-19: Coronavirus disease 2019; AFR: African region; AMR: Americas region; EMR: Eastern Mediterranean region;
EUR: European region; SEAR: South-East Asia region; WPR: Western Pacific region.
Complete data for the Eastern Mediterranean region were available only up to the eighteenth epidemiological week for the year 2024 (during the data extraction period).
Source: Data from WHO7 (Appendix 1 - supplementary material).
For the other sections of the manuscript, literature searches were performed to retrieve relevant articles related to the topic of the study. Five academic literature databases were searched: CINAHL, MEDLINE/PubMed, Web of Science Core Collection, Scopus, and Google Scholar. The searches were conducted by combining keywords related to COVID-19, SARS-CoV-2, pandemics, long COVID, scientific misinformation, and health surveillance, using the Boolean operators AND, OR, or NOT. The most recent, relevant, and reliable scientific articles found were considered and included in the present study.
Study Definition
Expected cases: the number of possible affected individuals resulting from the difference in COVID-19 cases expected to be registered due solely to variations in testing frequency, based on estimates from the same period of the previous year.
Trends and challenges in COVID-19 reporting: a comparative analysis of global cases from 2022 to 2023
Based on a general and comparative analysis of the situation of the COVID-19 pandemic in the period between the first 4 months of 2022 and 2023, a considerable decrease in the number of confirmed cases of the disease can be observed (Table 1); although the problem of underreporting may have been even more prevalent in 2023. In Europe, and the Eastern Mediterranean and South-East Asia regions, the difference between the number of expected cases and the number of cases registered for the first 4 months of 2023 was found to be quite evident, with decreases close to 50%. This decrease can be observed to be even greater in the case of Africa (Table 1), which may mean that, even considering the possible problem of underreporting,Reference Thenon, Peyre and Huc8 the disease prevalence may have actually been reduced in such regions.
On the other hand, based on the findings obtained, the same cannot be said for the Americas and Western Pacific regions. In the Americas, the number of cases registered in the first 4 months of 2023 was found to be almost 6 times the number of the expected ones, which may represent an important point of concern. In the Western Pacific region, an even more serious situation occurred in the same period with the registered cases being 27 times the expected ones (Table 1). Therefore, it is plausible to think that these 2 regions may still have represented an important and challenging cluster of COVID-19 during the beginning of 2023.
It is worth highlighting, however, that the set of these estimates might be considered potentially optimistic for all regions compared to the actual situation. This is because the strong reduction in screening tests (Table 1) may result in a higher percentage of people in the population who were not tested and who, however, may be infected/diseased, further increasing the chances of underreporting.
Through this first analysis, it is possible to illustrate the peculiarities of the COVID-19 situation in the period close to the declaration of its end as a PHEIC. The next section of the manuscript addresses the second analysis strategy and further related discussion.
More on the past, and current and future perspectives
According to the findings based on our second analysis strategy, which are reported in Figure 1 A-R, it is possible to highlight how the average number of confirmed COVID-19 cases has decreased substantially worldwide from 2022 to 2024 in a suggestively uniform manner. This, in turn, is likely the result of a combination of factors, including but not limited to robust public health measures implemented and mass vaccination campaigns.7 However, potential seasonal variations can be observed in most of the WHO regions, with the highest number of cases usually occurring at the beginning of each year (during the months of January and February), as evidenced especially in Africa (Figure 1 A, D, and G), Europe (Figure 1 J, M, and P), and the Americas (Figure 1 B, E, and H).
All regions, with the exception of the Western Pacific region (Figure 1 L, O, and R), experienced a potential significant peak in the number of COVID-19 cases during the first months of 2022, likely related to the spread of the Omicron variant along with a possible situation of distrust in vaccination involving part of the world population.Reference Karafillakis, Van Damme and Hendrickx3 On the other hand, the estimates for Africa (Figure 1 A, D, and G) show a much lower total number of cases compared to the other regions throughout the entire period analyzed, which could mainly be attributed to possible evidence of significant underreporting and lower testing rates,Reference Thenon, Peyre and Huc8 in addition to the potential influence of higher temperatures and solar radiation.Reference Vandelli, Palandri and Coratza9 Despite this, the overall trend in the number of cases shows similarities to other regions, such as the Americas (Figure 1 B, E, and H) and Europe (Figure 1 J, M, and P).
The Americas, as mentioned previously, showed a significant peak in early 2022 with around 30 million cases in the first month, followed by a gradual and consistent decline over the years (Figure 1 B, E, and H, Appendix 1 - supplementary material7). In contrast, the Eastern Mediterranean region showed a less defined trend throughout the analyzed period, with important and different peak periods (Figure 1 C, F, and I) compared to the typical periods observed in Europe (Figure 1 J, M, and P), the Americas (Figure 1 B, E, and H), and Africa (Figure 1 A, D, and G). Europe, despite its smaller population, was found among the regions with the highest number of cases, which could be related to the higher population densities.Reference Vandelli, Palandri and Coratza9, Reference Mogi and Spijker10 In this case, peak periods occurred in early 2022 and 2023 (Figure 1 J and M), with around 40 million and 1.5 million cases in January of each year, respectively (Appendix 1 - supplementary material7). Such identified characteristic variations may represent a seasonal pattern of disease peaks.
The estimates presented further suggest that the South-East Asia region may have been affected by almost 7 million cases in January 2022. However, despite this initial peak, the number of cases shows a substantial decrease throughout the study period, with the total number of cases considered relatively very low (Figure 1 K, N, and Q) compared to other regions (despite the large population living in this region).Reference Unnikrishnan, Mangalathu and Kutty11 Similar to Africa,Reference Thenon, Peyre and Huc8, Reference Vandelli, Palandri and Coratza9 the cause of this finding could be related to the weaknesses of health systems and underreporting of COVID-19 cases,Reference Unnikrishnan, Mangalathu and Kutty11 in addition to a potential influence, among other factors, of higher temperatures and solar radiation.Reference Vandelli, Palandri and Coratza9 The Western Pacific region was also found to have been affected by an important number of cases. With a different trend in the year 2022 compared to other regions, a significant increase in the number of cases can be observed for the Western Pacific region towards the end of 2022 (Figure 1 L), with more than 83 million cases reported (Figure 1L, Appendix 1 - supplementary material7). Despite this, the trend from late 2023 until September 2024 shows a gradual decline (Figure 1 O and R).
Within this context, an important observation should be done concerning the decrease in the number of COVID-19 cases. Indeed, despite this initially encouraging trend, considerable and often cyclic fluctuations in the number of reported cases can be observed in all regions considered (Figure 2 A-F). The Eastern Mediterranean, South-East Asia, and Western Pacific regions specifically exhibit a sharp increase in specific weeks (Figure 2 C, E, and F, respectively), which could be related to sporadic outbreaks and/or increased testing demand. However, the occurrence of smaller variations in the percentage increase in the number of cases reported over the years/months analyzed, especially in the Americas and Europe (Figure 2 B and D), may suggest that more satisfactory surveillance and monitoring systems might have been implemented with the lessons learned from previous years of the pandemic.
Nevertheless, the lack of a fully established trend for the potential seasonality of the disease in most regions and the possibility of unpredictable peaks should still be a point of interest and concern for health authorities and other key stakeholders. Such data should therefore serve as a stimulus for a review or implementation of new and/or more accurate related measures, such as case monitoring and identification of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, to predict the occurrence of such outbreaks/peaks of cases more assertively. Understanding these issues in more depth may also allow for more efficient vaccination strategies with the potential to even prevent or at least partially mitigate such peaks of infection, as happened in 2022 with the spread of the Omicron variant.12 In view of this, it should be essential and timely for all countries to learn, adapt, and prepare to maintain control of COVID-19 in their territories, as well as to face future pandemics and new outbreaks of other infectious diseases.Reference Tovani-Palone, Doshi and Pedersini13 Details of other related issues and further recommendations for possible solutions and the need for additional measures to better deal with this unpredictability are discussed below.
General Aspects of SARS-CoV-2 and Long COVID
Of great importance to this discussion, the COVID-19 causing virus, SARS-CoV-2, has undergone several mutations since the beginning of the pandemic, resulting in the emergence of different variants. Among the notable SARS-CoV-2 variants are the Alpha variant, Beta variant, Gamma variant, Delta variant, and Omicron variant. Due to their higher transmissibility and potential to cause more serious illness than the original virus, all these mutated strains have been raising additional concerns around the world. The WHO has been monitoring all known SARS-CoV-2 variants through the Virus Evolution Working Group and the Technical Advisory group on SARS-CoV-2 Virus Evolution. Based on their possible impact on community health, 4 types of classifications are being considered for surveillance, including variants of interest, variants of concern, variants of high consequence, and variants being monitored.14, 15 From this perspective and the preliminary findings of this study, SARS-CoV-2 and its variants continue to represent an important threat to the health of the population whether in terms of acute infections (or reinfections) or with respect to post-acute sequelae. This is true even with the present control of the pandemic situation on a global scale.Reference Jassat, Reyes and Munblit16
Another growing challenge in this context is the post-acute COVID-19 sequelae, which can involve multiple organ systems associated with varied signs and symptoms, including fatigue with or without exertion, myalgia, shortness of breath, glucose intolerance, postural orthostatic tachycardia, peripheral neuropathy, and multisystem inflammatory syndrome, among others.Reference Nikolich and Rosen17 However, this condition has been addressed in the literature using different terminologies, such as “long COVID,”Reference Nikolich and Rosen17 PASC (post-acute sequelae of COVID-19),Reference Lineburg and Smith18 and PCC (post-COVID-19 condition).Reference Warren-Gash, Lacey and Cook19, Reference Pazukhina, Andreeva and Spiridonova20 In order to standardize the related case definition, in October 2021, a Delphi consensus-based clinical definition of PCC was introduced by the WHO stating that “Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis”.21
Continuing on the subject, and with an outstanding concern about this, more recently members of a highly reputed committee and their lead staff proposed the 2024 NASEM long COVID definition, considering the following definition for the condition “Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems”.Reference Ely, Brown and Fineberg22
Despite notable advances in both the prevention of COVID-19 through mass vaccination of the population and in the management of affected patients with the use of different pharmacological agents, it is still expected that long COVID will affect 10% or more of infected patients.Reference Nikolich and Rosen17 With many studies still ongoing, long COVID complications have been linked, in particular, to 2 mechanisms: (1) dysregulated production of inflammatory cytokines and (2) the persistence of SARS-CoV-2;Reference Lineburg and Smith18 however, even more discoveries are needed to clarify these pathways in more detail as well as various other aspects of the pathophysiology of COVID-19 and its different and subsequent complications/outcomes.Reference Bistagnino, Pizzi and Mantovani23
Considerations and Controversies on Epidemiological Research Addressing Long COVID
Although a quick search in the Scopus and PubMed databases makes it possible to find studies on long COVID using robust methodology, such as based on different methods (including updated Delphi consensus),Reference Warren-Gash, Lacey and Cook19, Reference Pazukhina, Andreeva and Spiridonova20 there are still important gaps to be filled with regard to the related epidemiology because most of the studies about this subject were performed before the 2021 WHO consensus. Despite this, comparing, for example, post-COVID-19 symptoms (PCS) and symptoms found in PCC, a great overlap can be observed.Reference Chakrovorty, Hossain and Shafin24 As a result, the most important features which should be considered by research addressing long COVID are not just the symptoms per se (which are extremely heterogeneous), but the timing of their onset and the length of their persistence, as it was intuited and proposed by Fernández-de-Las-Peñas et al.Reference Fernández-de-Las-Peñas, Palacios-Ceña and Gómez-Mayordomo25 before PCC definition by WHO.
This is also in line with the study by Alkodaymi et al.Reference Alkodaymi, Omrani and Fawzy26 In an important contribution on the analysis of PCC symptoms heterogeneity and persistence, quite aligned with the respective WHO definition, these authors considered the inclusion of studies with a minimum follow up of 12 weeks and up to 12 months or more. From this manuscript, again, it is possible to infer how symptoms are quite consistent and redundant over time, highlighting the role of timing in long COVID definition rather than just the symptoms.
Scientific Misinformation Related to the Pandemic
Another point that deserves to be highlighted is the problem of scientific misinformation. First, we understand that the pandemic period has been quite troubled and challenging, whether for political, economic, or social reasons. Second, during such period, failures in health system management worldwide have been identified in parallel with the publication of a growing number of scientific articles that incite the issue of scientific misinformation related to COVID-19.Reference Tovani-Palone4 In light of this, it is imminently important for researchers in the field to be aware of carefully substantiating research questions stated in their manuscripts as well as the conformity of the content described, thereby contributing towards the fight against scientific misinformation that has possibly been extrapolated. The absence of such caution can have the capacity to stimulate the catastrophic effect of the lack of appropriate health planning associated with other related issues, which can lead to worse outcomes and scenarios. Such impacts certainly have the potential to affect both the context of vaccination and the appropriate use of medicines and case management, and therefore have a high probability of hindering the mitigation of COVID-19.
Recommendations to Prevent Further COVID- 19 Spreads and Optimize Case Management
Further advancing the discussion about the COVID-19 situation and related propositions, it should be noted that in the past decades, the world has experienced the spread of different virus strains which strongly threatened the population, such as Ebola virus (2014-2016), Middle East respiratory syndrome coronavirus (MERS-CoV) (2012), and influenza A (H1N1) (2009). However, what has especially characterized SARS-CoV-2 infection is the rapidity of transmission of the virus, the related high morbidity rate, and the large number of deaths on a global scale. This pattern of features is best represented by R0 index, which expresses the average number of new infections generated by 1 infected individual. This value is particularly high in the case of SARS-CoVReference Achaiah, Subbarajasetty and Shetty27 (often higher than 2, but it has also been often reported above 3) compared to MERS-CoV and H1N1 influenza, for instance.Reference Liu, Xie and Wang28, Reference Coburn, Wagner and Blower29
Therefore, an important point in preventing SARS-CoV-2 spread might be the implementation of continuous health surveillance programs very similar to those existing for tracking the influenza virus, such as the Global Influenza Surveillance and Response System (GISRS) and the European Influenza Surveillance Network (EISN). This could indeed positively impact several aspects of management of potential SARS-CoV-2 spreads.
Moreover, the existence of efficient tracking systems would allow early identification of SARS-CoV-2 clusters, as well as better understanding of their evolution, contributing to the implementation of updated therapeutic approaches. Alam et al.,Reference Alam, Radovanovic and Incitti30 for instance, designed CovMT, which is a mutation tracker system that gathers information related to the mutations on the spike’s protein receptor binding domain, RBD, as well as about the location of registered mutations and disease severity.
However, in addition to tracking the prevalence and spread of SARS-CoV-2 and its variants, it would be extremely helpful to also predict mutations in the viral genome. Zhou et al. focused on this topic and elaborated a transformer-based mutation prediction framework (TEMPO), which demonstrates the feasibility of the employment of such models in the prediction of the variants that will be encountered with the highest likelihood.Reference Zhou, Zhou and Zhang31 Based on this perspective, an effective prediction model combined with the versatility of messenger ribonucleic acid (mRNA) vaccines might represent a key and decisive step in COVID-19 disease prevention.
Apart from continuing surveillance, vaccination campaigns and actions to combat the infodemic are other crucial steps in containing the spread of SARS-CoV-2. Vaccines are undoubtedly the most important tools science has developed to prevent viral diseases and their key role has been clearly demonstrated during the COVID-19 pandemic. Marcellusi et al. analyzed the effect of COVID-19 vaccine administration in Italy and found that around 71.3% of admissions to intensive care units and 74.9% of hospitalizations were preventable compared to a scenario without vaccination.Reference Marcellusi, Fabiano and Sciattella32
This is also relevant in terms of reduction of the economic resources needed to provide adequate patient care. Indeed, it has been estimated that COVID-19 vaccines have saved billions of dollars around the world. Therefore, it seems plausible that the maintenance of large specialized permanent departments for COVID-19 may be unsustainable in the long term and that the combination of screening and predicting of SARS-CoV-2 variants together with the design of updated vaccines could represent a possible solution to, at least, achieve and maintain effective and satisfactory control over COVID-19.
Limitations and Strengths
The present study has limitations. The estimates of the expected number of cases presented in Table 1 were obtained based on the influence of only 1 variable, variation in COVID-19 testing frequency, and without the use of complex mathematical models. As a result, other possibly influencing factors, such as immunity due to previous infection or vaccination, were not possible to be estimated together. In addition, complete data on the number of confirmed COVID-19 cases for the months included in 2024 regarding the Eastern Mediterranean region (used for our second analysis strategy) were only available up to the eighteenth epidemiological week, thus limiting the achievement of a complete analysis for this region compared to the others. Finally, although the WHO COVID-19 dashboard data used in this study are subject to constant revisions and/or updates over time, it was possible to contextualize the COVID-19 situation within the proposed objectives and time periods and years considered for each analysis performed. Considering this, the results of our estimates should represent insightful perspectives that express above all the authors’ point of view based on the data available from the WHO in each period of interest (during the mentioned data extraction periods). Furthermore, the content discussed may represent valuable knowledge for different actors, including public health stakeholders, especially policy makers.
Final Consideration
Continuous efforts and implementation or maintenance of health programs aimed at maintaining control of COVID-19 around the world are crucial to be carried out, especially those supported by governments, health authorities, and pharmaceutical companies. This includes the availability of tests for COVID-19, and related medicines and vaccines. Moreover, more efforts are needed towards the development of new versions of COVID vaccines that provide longer-lasting and broader immunity against SARS-CoV-2, as well as further exploration into the design and development of combination vaccines that protect against COVID-19 and other respiratory infections. Finally, combating vaccine hesitancy and the associated infodemic are 2 other imminently important steps to be taken in order to improve the current situation while contributing to the Sustainable Development Goals.
Supplementary material
The supplementary material for this article can be found at http://doi.org/10.1017/dmp.2025.10.
Data availability statement
Secondary data used in this article are included in the article and/or referenced in the article and/or in supplementary material. Any additional datasets may be requested from the corresponding author upon reasonable request.
Author contribution
Conceptualization, writing-reviewing and editing, data analysis and interpretation, project administration and designing: Marcos Roberto Tovani-Palone (MRT-P) and Filippo Bistagnino (FB); Data extraction: FB; Supervision: MRT-P; Manuscript writing: All authors; Final approval: All authors.
Ethical standard
Data used for this manuscript correspond to secondary data obtained from the WHO COVID-19 dashboard, which is a publicly available database, and therefore approval by an Ethics Committee was not required.
Acknowledgments
MRT-P thanks the Saveetha Institute of Medical and Technical Sciences, while Arunkumar Subramanian thanks the SRM Institute of Science and Technology for supporting this study.
Funding statement
Not applicable.
Competing interest
All the authors report no relevant conflicts of interest for this article. MRT-P discontinued his affiliation with SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, India.
