Resurging COVID-19 as a global concern, and the role of artificial intelligence: what it means for healthcare measures including oncology?

Abstract

Introduction Fresh persistent presence of COVID-19 that has emerged recently has shaken the world as it had just begun to breathe easy after the worst pandemic in human history. According to the WHO, the recent positivity rate reached 11% for the first time since July 2024 [1]. Following a spike in COVID-19 in many Southeast Asian countries, a surge in confirmed reports with nearly thousand new COVID cases was recorded across India recently since 12 May 2025. India witnessed fresh COVID cases in several provinces recently. The number of reported cases crossed a thousand in India by May last week, as officially confirmed (https://covid19dashboard.mohfw.gov.in/). It was encouraging that most cases were mild (low on severity and mortality). Recently, KEM Hospital, Mumbai confirmed two COVID-related deaths (https://www.freepressjournal.in/mumbai/mumbai-2-deaths-due-to-covid-reported-at-kem-hospital-in-parel-doctors-blame-comorbidities) which prompted a localized concern. The two deaths in KEM Hospital Mumbai had comorbidities, one was a 14-year old child with kidney failure and the other was a cancer patient of 54 years. Although not alarming yet, the uptick comes at a time when the two happening Southeast Asian countries (Singapore and Hong Kong) battled the fresh COVID waves. Singapore saw a 28% rise in weekly cases, while Hong Kong reported 31 COVID-related deaths which was its highest in a year (https://timesofindia.indiatimes.com/life-style/health-fitness/health-news/covid-cases-rise-in-singapore-and-hong-kong-important-things-to-know-about-the-new-variant/articleshow/121260200.cms#:~:text=Similarly%2C%20Hong%20Kong%20is%20experiencing,marking%20a%20one-year%20high). The COVID-19 cases are globally rising in Asia, including in South Korea, Singapore, China and Thailand. In its first update in the month of May this year on COVID-19 infection cases in almost a year, the state health ministry of Hong Kong estimated that the number of COVID-19 cases jumped 28% to 14 200 in the week through May 3, while daily hospitalization rose around 30% (https://economictimes.indiatimes.com/news/new-updates/another-covid-wave-coming-hong-kong-and-singapore-report-sharp-jump-in-cases-as-virus-detected-in-sewage-water/articleshow/121205235.cms?from=mdr). The coronavirus was very active in Hong Kong, and the percentage of respiratory samples testing COVID-positive there recently reached its highest in a year. In the city of Hong Kong with over 7 million, the data showed that severe cases reached their annual highest level. The COVID-related medical consultations and hospitalizations, and rising viral load in sewage water suggested that the virus was actively spreading there. Similar was the situation in Singapore. While the increase in cases there might be due to factors like waning herd immunity, Singaporean health ministry said that there was no indication that the circulating variants were more transmissible. The mounting number of confirmed cases in Singapore and Hong Kong came at a time when COVID rose across the Southeast Asia region in the past few months, with periodically swelling waves. Health authorities across the region have called on the citizens to update their vaccinations, and recommending booster shots for the high-risk individuals. As per the Chinese CDC (Centre for Disease Control and Prevention) data, China was on track to experience a fresh wave similar to the summer peak last year. The COVID positivity rate more than doubled in the 5 weeks through 4 May among the patients seeking a diagnosis at hospitals across the Chinese mainland. The Department of Disease Control in Thailand also had reported two cluster outbreaks this year. The primary focus of this article was to analyze the resurgence of fresh outbreaks of Corona due to the emerging novel SARS-CoV-2 subvariants in 2025 especially in Asia (with specific focus on India, Singapore and Hong Kong), understanding the transmission characteristics, immune escape patterns, and clinical symptoms of the novel JN.1 subvariants LF.7, NB.1.8 and its progeny lineages. The objective was to assess whether this community health concern posed a global public health threat, and the necessity to recommend targeted prevention and control measures (like strengthening vaccination for the high-risk groups, COVID-appropriate protective actions at the individual levels, etc.) based on this. The aim was also to provide empirical references for public healthcare decision-making to cope with the fresh waves. The authors have ensured that the article complied with the TITAN Guidelines 2025 – governing declaration and use of AI[2]. Novel Omicron subvariants Driven reportedly by the novel Omicron subvariants LF.7 and NB.1.8 (from JN.1 lineage) this time, the symptoms were mild, like sore throat, coughing, fever and fatigue. As in Southeast Asia, the situation was equally worrisome in India. Although the cases were sporadic, the JN.1 subvariant was believed to be behind the surge in India too as it had already registered its presence. Known as the “Pirola” strain of the Omicron, JN.1 variant descended from the Omicron BA.2.86. With immunity-evasion ability of its parent, mutated JN.1 transmitted and spread efficiently. It is to note that, BA.2.86 allegedly never dominated in 2023 among all the SARS-CoV-2 variants. Discovered in August 2023, JN.1 had acquired the ability to transmit efficiently through a couple of additional mutations. This variant contained around 30 immunity-evading mutations, more than any other circulating variant. Symptom-wise it has not differed much from the Omicron so far; however, it was more transmissible and could evade existing immunity. There were suggestions that JN.1 might cause more diarrhea than the earlier variants. BA.2.86 and JN.1 differed in that the latter had one mutation (a single change) in its spike protein. Although it may or may not alter any of the traits that characterized the virus, preliminary investigation revealed that it may provide extra immune evasion[3]. As also indicated above, the JN.1 symptoms are dry cough, loss of taste or smell, headache, runny or clogged nose, exhaustion, sore throat, fever and others, comparable to other SARS-CoV-2 variants. The COVID devil is not buried yet as its occurrences was still being reported worldwide. BA.2.86 (Omicron subvariant), a JN.1 strain descendant was earlier classified as the variant of interest, not as variant of concern, by the World Health Organization (WHO) maintaining that the global public health risks by JN.1 were low. Singaporean health authorities stated that new JN.1 descendants LF.7 and NB.1.8 were circulating rapidly there. As per the health minister there, the country was expected to experience periodic COVID-19 waves round the year. The occurrence of the increasingly transmissive and infective JN.1 descendants LF.7 and NB.1.8 could seize the world with another wave of the resurged COVID pandemic. The comeback of COVID-19 at a time when the northern hemisphere enters summer demonstrated that the virus could still sicken a large population (and affect the overall human productivity) even when the weather was hot, unlike other respiratory pathogens. Reports on the spillover and spillback instances of LF.7 and NB.1.8 are still awaited, and if that occurs, God forbidden, the situation is bound to go out of control again. The health authorities across nations, therefore, have urged their citizens to stay updated on vaccinating themselves and take necessary COVID-appropriate precautions (like personal hygiene, social distancing and face-masking). Genetic mutations The NB.1.8.1 and LP.8.1 variants had additional spike mutations F59S, G184S, A435S, V445H, T22N, and T478I as compared to the currently dominant SARS-CoV-2 variant. NB.1.8.1 had T22N, F59S, G184S, A435S, L455S, F456L, T478I, and Q493E in comparison to JN.1 (https://cdn.who.int/media/docs/default-source/documents/epp/tracking-sars-cov-2/23052025_nb.1.8.1_ire.pdf). Spike mutations at position 445 reportedly enhanced the binding affinity to hACE2, which might enhance the transmissibility (faster human-human spreading) of the variants. Mutations at position 435 demonstrated reduced neutralization potency of class 1 and class 1/4 antibodies[4], and mutations at position 478 enhanced the evasion of Class 1/2 antibodies[5]. Though preliminary risk assessment of the WHO classified NB.1.8.1 as of low public health risk, the A435S, V445H and T478I spike protein mutations suggest increased transmissibility and immunity evasion ability. NB.1.8.1 circulation increased and reached 10.7% of the global sequences reported till the mid of May[1]. Although the recent rise in COVID-19 cases is broadly consistent with the levels observed during the same period in the previous year, a clear seasonality in SARS-CoV-2 circulation is not evidenced, and therefore the surveillance is also limited. Close monitoring and further research are essential to understand the transmission dynamics of these two new variants (NB.1.8.1 and LP.8.1) thoroughly and prepare ourselves cautiously as the situation unfolds. Effect on the healthcare system related to oncology COVID-19 pandemic also has had its toll on the cancer-care aspects like patient diagnosis and follow-up therapies that led to increasing mortalities, primarily attributed to the limited access to the healthcare services. Case identification or registration of patients comparatively fell sharply during the pandemic period[6]. Managing cancer patients during the period was awfully hard while such patients required special attention being immunocompromised and severely COVID-vulnerable due to several anticancer measures to treat malignancies[7]. Also, physicians resorted to alternate ways to treat cancer without compromising the outcomes and reduce visits to hospitals, hospitalization and immunity-related adverse effects. Significantly delayed diagnosis and treatment of cancer could adversely affect the outcomes like reduced effective treatment, increased suffering, less survival chance and higher morbidity[8]. Since cancer therapy needed a multidisciplinary strategy depending on the disease stage and severity, it was essential to develop excellent alliance across departments like emergency, radiation, surgical and medical oncology. During this period, the patient was also required to receive appropriate COVID protection and safety. Vaccination and challenges Vaccines continue to offer protection against hospitalization and severe illnesses in the wake of new variants. Vaccination helps fight a disease better in the wake of continued infections by mutated viruses. Booster doses top up this protection, especially among the elderly and those with comorbidities. However, the overall COVID-19 vaccine coverage reportedly remained low global with significant disparities across regions and income levels, particularly among the high-risk groups[1]. As per the estimate, only about 1.68% older adults received only a single dose in 2024, up to 30 September 2024[1]. Although no vaccine is 100% effective, keeping updated on immunization could reduce the instances of complications while enhancing the herd immunity and curb spread of the infection. The suggested precautions at individual and households levels are, face-masking in crowded places, frequent sanitization of hands, volunteering for vaccination and boosters as per the advisory, taking post-vaccination precautions (not neglecting symptoms like cough or fever), isolating (quarantine) of self on encountering credible symptoms, refraining from self-medication without consulting a practicing doctor, and staying indoors as much as practicable when sick. It was time to prepare and stay alert (and not alarmed) before the situation was out of control. Though the current numbers are low and the situation is not panicking in majority of the places across the globe, continued monitoring, vaccination and sanitization practices could prevent the occurrence of another wave. Experts from the Emergency Medical Relief division, Disaster Management Cell, National Centre for Disease Control, Indian Council of Medical Research (ICMR) and the Central government hospitals in India reviewed the situation in India on 19 May 2025, chaired by the Director General of Health Services. With no large-scale resurgence indicated, health officials (including the representatives from ICMR and NCDC India) opined that the overall situation in India was under control. However, the experts cautioned against complacency, urging the “high risk” regions of Southeast Asian region including India to follow safety protocols. Enhanced surveillance, early detection and response mechanisms were allegedly in place in India as precaution. The new variants NB.1.8.1 and LF.7 were responsible for the current surge, as per the Indian Health Ministry. These variants contributed over the past few weeks to the surge also in China, Singapore and Hong Kong. The WHO classified them under the variants under monitoring category. The two new variants NB.1.8.1 and LF.7 circulating rapidly these days were the descendants of JN.1 variant, the associated symptoms remaining similar to Omicron strain. Although current data did not indicate that these variants led to severe illness, the data were limited to draw any foolproof conclusion. Although the cases remained mild, healthcare experts and researchers opined that boosters and precautions for the high-risk groups were recommended. The NB.1.8.1 and LF.7 variants might evade immunity especially in people who did not receive booster shots. Alongside immune evasion trait due to the distinct gene mutations in the viral spike protein, seasonal conditions and human behavior were possibly the other driving factors behind the spread of these variants. The COVID-19 causative agent SARS-CoV-2 has mutated over time as seen in the last 4 years of the early and post pandemic phase, resulting in genetic variation, which affected transmission and severity of virus[9,10]. These mutations conferred resistance in the strains against antiviral drugs, thereby posing challenges to treat effectively[11]. Although COVID-19 pandemic was no longer a global emergency, continued research on analyzing the complex interactions between the virus and the host remained crucial, particularly for a more nuanced and adaptable strategy to manage drugs resistance in immunocompromised and high-risk subjects[12]. In this context, adoption of a multifactor approaches like combinatorial therapies, drug repurposing, drug repositioning and targeted drug development, and continual surveillance of the mutating virus, through collaborative initiatives among the scientists, biopharmaceutical industry, and global health agencies was essential to counter the challenges. The current dramatic increase in COVID-19 cases at global scale suggested that both vaccination (active immunization) and herd immunity (passive immunization) might not be able to eliminate the COVID-19 virus SARS-CoV-2 or establishing a persistent immunity against the virus[13]. It is known that the currently administered vaccines against COVID-19 were developed and approved for “emergency use,” without much knowledge about the epidemiology, the viral form, viral mutations, human response to the vaccines, reinfection or reactivation of the infection, coinfections, and the spillover and spillback infection aspects. In view of this, it was highly recommended that the health agencies and scientific communities establish future targeted R&D plans to seek further path-breaking sustainable solutions, not only to solve the prevailing situation but also toward preventing future pandemic. Another critical challenge in pursuing the vaccination drive is vaccine equity (equitable distribution of the vaccines worldwide) as low and medium income countries (LMICs) still faced challenges in equitable vaccine delivery. To address this issue, COVAX initiative was launched by the WHO and its partners with “no one was safe, until everyone was safe” guiding principle to provide equitable access to the vaccines across LMICs[14], although the regional disparities in vaccine distribution could still persist. Hence, it was suggested to develop and implement tailored (region-specific) strategies for equitable distribution and prepare for health emergencies in future[15]. Artificial intelligence (AI) for pandemic management and response Caused by SARS-CoV-2, COVID-19 spread across the globe that affected more than seven hundred millions and claimed nearly seven million lives in the past more than 4 years, and cost billions of dollars. As witnessed, this highly infectious disease could easily overwhelm the healthcare systems, if not managed swiftly. Also the existing diagnostic techniques were less sensitive[16]. Developments in artificial intelligence (AI) could potentially be an effective option to manage and develop response against the pandemic, particularly through improved prediction of the infection and transmission patterns, contact-tracing, screening of the subjects, diagnosis of suspected cases, treatment of the confirmed cases, medication options, follow-up during convalescence, the development of COVID-19 vaccines, and reduced human intervention in medical practices[17]. The AlphaFold AI model developed recently could be applied in molecular biology and drug discovery[18]. The clinical image-based AI models provided significant predictive values for disease management and individualized treatments[19]. Breaking the black-box of virus evolution AI-driven gene sequence analysis could analyze transmission paths and recombination patterns of the mutant strains across regions on a real-time basis, and accurately predict highly vulnerable mutation sites, as for instance the effect of T478I mutation of the spike protein, thereby compensating for the shortcomings of the current “passive monitoring – lagging response” model. Deep learning-based protein structure prediction (for instance by AlphaFold model) could reconstruct the vaccine and drug development paradigm and accelerate the designing of multivalent vaccines against emerging mutants. Also, the generative AI could simulate molecular interactions among the mutant strains and the antiviral drugs, shorten the development cycle of a potential drug candidate by one-tenth as against the conventional approaches. Constructing a dynamic and precise prevention and control system Combining the multi-source data (clinical imaging, sewage monitoring, mobile trajectory) AI early warning model enabled identifying early outbreak (through predictive value of the viral load surge in the sewerage system in vulnerable areas). Also, the individualized risk stratification tools that integrated age, the underlying disease (comorbidities), the immunization history, etc. could optimize resource allocation in the targeted areas with limited medical infrastructure. Key research directions AI-based models could be developed for intelligent strain prediction. AI model that established an early warning system by integrating global viral genome libraries could a from the “passive to an AI models could be applied on the through that targeted at prevention and control strategies by the of community health (like the of a vaccine AI-based assessment models could also the vulnerable population like cancer patients through and predictive for the patients under with COVID-19 to the in such vulnerable of AI in management and research on infectious from to the – precise is a and value in the such as resource delayed healthcare response and diagnosis through conventional public healthcare options, to provide the to a health AI-driven could control and the public healthcare in a such aspects and research could provide directions for in medical with Although there were several additional collaborative multidisciplinary actions that and in and AI against COVID-19 infections and future community emergencies were

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