Editorial: Infectious Disease Surveillance Using Artificial Intelligence (AI) and its Role in Epidemic and Pandemic Preparedness.

Artificial intelligence (AI), or machine learning, is an ancient concept based on the assumption that human thought and reasoning can be mechanized. AI techniques have been used in diagnostic medicine for several decades, particularly in image analysis and clinical diagnosis. During the COVID-19 pandemic, AI was critical in genome sequencing, drug and vaccine development, identifying disease outbreaks, monitoring disease spread, and tracking viral variants. AI-driven approaches complement human-curated ones, including traditional public health surveillance. Preparation for future pandemics will require the combined efforts of collaborative surveillance networks, which currently include the US Centers for Disease Control and Prevention (CDC) Center for Forecasting and Outbreak Analytics and the World Health Organization (WHO) Hub for Pandemic and Epidemic Intelligence, which will use AI combined with international cooperation to implement AI in surveillance programs. This Editorial aims to provide an update on the uses and limitations of AI in infectious disease surveillance and pandemic preparedness.

Editorial: The XBB.1.5 ('Kraken') Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread.

In November 2021, the World Health Organization (WHO) first identified the Omicron variant of SARS-CoV-2, B.1.1.529, as a variant of concern (VOC). By early 2022, the Omicron variant and its five lineages, BA.1, BA.2, BA.3, BA.4. and BA.5, had become the predominant cause of COVID-19 in most countries. The Omicron XBB.1.5 subvariant is a sublineage of the XBB variant, a recombinant of two BA.2 sublineages, with the F486P mutation in the spike protein that increases infectivity due to increased binding affinity to the angiotensin-converting enzyme 2 (ACE2) receptor. On the week ending 21 January 2023, the XBB.1.5 subvariant caused 49.1% of cases of COVID-19 in the US. The rapid rise in the prevalence of this subvariant may be explained by immune escape to previous infection or vaccines, spike mutations in F486P, and increased affinity for the ACE2 receptor. Also, current booster vaccines may not provide adequate protection from infection from this subvariant, which has been named by the media as the 'Kraken' subvariant. This Editorial aims to present the current status of the XBB.1.5 subvariant of Omicron SARS-CoV-2 and the reasons for, and implications of, its rapid global spread.

Editorial: The World Health Organization (WHO) Fungal Priority Pathogens List in Response to Emerging Fungal Pathogens During the COVID-19 Pandemic.

The COVID-19 pandemic, climate change, increased resistance to antifungal drugs, and an increased number of immunocompromised patients have driven a recent global surge in pathogenic fungal infections, including aspergillosis, candidiasis, and mucormycosis. On 25 October 2022, the World Health Organization (WHO) released a list of 19 fungal priority pathogens identified as having the greatest threat to public health. The WHO Fungal Priority Pathogens List represents the first global response to identify and prioritize fungal pathogens and their impact on global public health and to consider the unmet research and development needs. The WHO has grouped the priority fungal pathogens into those of critical, high, and medium priority. This Editorial aims to highlight the importance of identifying and prioritizing fungal pathogens and identifying emerging fungal pathogens and the global factors driving changing patterns of infection.

Editorial: Rebound COVID-19 and Cessation of Antiviral Treatment for SARS-CoV-2 with Paxlovid and Molnupiravir.

One of the most recently described clinical associations with SARS-CoV-2 infection is rebound COVID-19, which occurs between five and eight days following the cessation of antiviral treatment. Most case reports of rebound COVID-19 have been associated with cessation of treatment with the combined oral antiviral agent nirmatrelvir/ritonavir (Paxlovid). On 24 May 2022, the US Centers for Disease Control and Prevention (CDC) issued a Health Alert Network (HAN) Health Advisory update for patients, healthcare providers, and public health departments on COVID-19 rebound or recurrence of COVID-19. However, population data from the US showed no significant differences in the risk of developing rebound COVID-19 between patients treated with Paxlovid and Molnupiravir. The mechanisms of rebound COVID-19 remain unclear but may involve the development of resistance to the antiviral drug, impaired immunity to the virus, or insufficient drug dosing. A further explanation may be the persistence of a high viral load of SARS-CoV-2 in individuals who are no longer symptomatic. This Editorial aims to provide an update on what is known about rebound COVID-19 and the current public health implications.

Editorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic.

The range of long-term clinical conditions following SARS-CoV-2 infection in adults is now recognized. However, the prevalence, presentation, and risk factors for long COVID, or post-COVID-19, in children are less well understood because there have been few follow-up studies or long-term clinical trials in children with COVID-19. However, recent studies have shown that children with mild or asymptomatic COVID-19 may develop long-term sequelae that include cough, fatigue, and lethargy. The incidence and severity of common childhood respiratory viruses have changed in the past year, including respiratory syncytial virus (RSV). Hepatitis of unknown cause in children with SARS-CoV-2 infection is increasingly reported. Although both a viral cause and an autoimmune cause have been proposed, adenovirus type 41 infection is of current interest. These findings support immunization programs for SARS-CoV-2 in children, and infection surveillance and monitoring of the changing patterns and severity of other pediatric viral infections, including adenovirus type 41 and RSV, to develop and administer effective vaccines. This Editorial aims to highlight what is currently known of the long-term effects of symptomatic and asymptomatic SARS-CoV-2 infection in children and the changing epidemiology and pathogenesis of previously common childhood viral infections now driven by the COVID-19 pandemic.

Editorial: World Health Organization (WHO) Variants of Concern Lineages Under Monitoring (VOC-LUM) in Response to the Global Spread of Lineages and Sublineages of Omicron, or B.1.1.529, SARS-CoV-2.

On 26 November 2021, the World Health Organization (WHO) identified the B.1.1.529 variant, or Omicron variant, as the fifth variant of concern (VOC) of SARS-CoV-2. The B.1.1.529 Omicron variant of SARS-CoV-2 includes five lineages, BA.1, BA.2, BA.3, BA.4. and BA.5. During the past six months, several identified sublineages of B.1.1.529 have rapidly spread globally. Although the lineages BA.1 and BA.2 initially predominated, BA.4, BA.5, and sublineage BA.2.12.1 are now dominant in Europe and the USA. On 12 May 2022, the European Centre for Disease Prevention and Control (ECDC) reclassified BA.4 and BA.5 from variants of interest (VOI) to variants of concern (VOC). BA.2.12.1, BA.4, and BA.5 have shown higher transmissibility and increased neutralization evasion compared with BA.2 when tested against plasma from patients with triple-vaccination and following infection with BA.1. On 7 June 2022, the World Health Organization (WHO) added a new category to its SARS-CoV-2 variant tracking system, the VOC Lineages Under Monitoring (VOC-LUM), which aims to inform global public health authorities of the VOC lineages and sublineages that may require prioritized attention and monitoring. This Editorial aims to present an update on the lineages and sublineages of the Omicron variant of SARS-CoV-2 and the VOC-LUM initiative from the WHO.

Editorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19.

The consequences of SARS-CoV-2 infection include short-term, long-term, mild, and severe clinical symptoms. The cardiovascular system, including endothelial cells, vascular smooth muscle cells, and cardiac myocytes, are important targets for SARS-CoV-2. In February 2022, the findings from a large US cohort of individuals diagnosed with COVID-19 and two sets of control cohorts evaluated the risk and 12-month cardiovascular disease burden. Individuals who had COVID-19 had a 72% increased risk of heart failure, a 63% increased risk of myocardial infarction, and a 52% increased risk of ischemic stroke compared with controls. These results were independent of gender, race, age, and other cardiovascular risk factors, including diabetes, obesity, hypertension, hyperlipidemia, and chronic kidney disease. As of 25 April 2022, the World Health Organization (WHO) reported that more than 80 million people in the US, more than 22 million people in the UK, and more than 505 million people worldwide were infected with SARS-CoV-2. This Editorial aims to present what is currently known about the cardiovascular outcomes at one year following SARS-CoV-2 infection and highlights that primary care physicians should be mindful of the COVID-19 infection status of their patients when evaluating cardiovascular health.

Editorial: First Approval of the Protein-Based Adjuvanted Nuvaxovid (NVX-CoV2373) Novavax Vaccine for SARS-CoV-2 Could Increase Vaccine Uptake and Provide Immune Protection from Viral Variants.

The Nuvaxovid™ (NVX-CoV2373) Novavax vaccine is a recombinant spike (S) protein nanoparticle vaccine combined with the Matrix-M adjuvant. On December 20, 2021, the European Commission of the European Union (EU) granted conditional marketing authorization for the Nuvaxovid™ (NVX-CoV2373) Novavax vaccine, following recommendations from the European Medicines Agency (EMA). On February 3, 2022, this vaccine was granted conditional marketing authorization (CMA) in Great Britain by the Medicines and Healthcare Products Regulatory Agency (MHRA) for use in individuals ≥18 years. The two vaccine components elicit both B-lymphocyte and T-lymphocyte immune responses to the S protein of SARS-CoV-2. The full-length S protein in this vaccine has common epitopes that could protect against all the SARS-CoV-2 viral variants. Also, the vaccine is stable and has a shelf life of 9 months when stored at standard refrigerated temperatures of between 2-8°C. This Editorial aims to present an update on the first approval of a protein-based adjuvanted vaccine for SARS-CoV-2, Nuvaxovid (NVX-CoV2373) from Novavax, and why it is such a significant development at this time.

Editorial: The 2022 World Health Organization (WHO) Priority Recommendations and Response to the Omicron Variant (B.1.1.529) of SARS-CoV-2.

The omicron variant of SARS-CoV-2, B.1.1.529, was included in the World Health Organization (WHO) list of variants of concerns (VOC) on 26 November 2021. Within only three months, omicron has spread rapidly to become the dominant variant in many countries. Studies have begun to evaluate the virulence, transmissibility, and degree of immune protection from current SARS-CoV-2 vaccines or previous of infection with the omicron variant. On 21 January 2022, the WHO published its seventh technical update and recommendations for priority actions in response to the omicron SARS-CoV-2 variant and cautioned that the overall risk from omicron remains high. At the start of this third year of the global COVID-19 pandemic, this editorial aims to summarize the evidence that supports the current priority recommendations and response from the WHO regarding the omicron variant of SARS-CoV-2, B.1.1.529.

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Patients.

On 4th November 2021, the first oral antiviral drug for COVID-19, molnupiravir (Lagevrio®), received full regulatory approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK. Molnupiravir is an orally bioavailable antiviral drug for use at home when a SARS-CoV-2 test is positive. On 22nd December 2022, the FDA granted emergency use authorization (EUA) for the oral antiviral drug, nirmatrelvir/ritonavir (Paxlovid®) for adults and children with mild and moderate COVID-19 at increased risk of progression to severe COVID-19. These regulatory drug approvals come at a crucial time when new variants of concern of the SARS-CoV-2 virus are spreading rapidly. Although the FDA approved remdesivir (Veklury®) on 22nd October 2020 for use in adults and children for the treatment of COVID-19 requiring hospitalization, its use has been limited by the requirement for intravenous administration in a healthcare facility. The four FDA-approved therapeutic neutralizing monoclonal antibodies, imdevimab, bamlanivimab, etesevimab, and casirivimab are costly and also require medically-supervised intravenous administration. The availability of effective, low-cost oral antiviral drugs available in a community setting that can be used at an early stage of SARS-CoV-2 infection is now a priority in controlling COVID-19. An increasing number of repurposed antiviral drugs are currently under investigation or in the early stages of regulatory approval. This Editorial aims to present an update on the current status of orally bioavailable antiviral drug treatments for SARS-CoV-2 infection.

Editorial: SARS-CoV-2 Vaccine Responses and Breakthrough COVID-19.

In 2021, data from global disease monitoring and infection surveillance programs have shown that vaccination programs have reduced the incidence of SARS-CoV-2 infection and hospitalization and mortality rates. Currently, the US Centers for Disease Control and Prevention (CDC) identifies a fully vaccinated individual as being ≥14 days after the completion of all the recommended doses of a COVID-19 vaccine that has been authorized by the US Food and Drug Administration (FDA). A partially vaccinated individual is <14 days following primary vaccination or has not completed the vaccination program. Clinical studies and data on the vaccine status of populations have identified breakthrough COVID-19 cases in fully vaccinated individuals at 14 or more days after completing the recommended dose of an authorized SARS-CoV-2 vaccine. This Editorial presents an update on what has been learned in the past year on SARS-CoV-2 vaccine responses and breakthrough COVID-19.

Editorial: What Can be Learned from National and International Vaccine Adverse Event Reporting Systems During the COVID-19 Pandemic?

Healthcare professionals have an ethical, medico-legal, and professional responsibility to report all suspected adverse events following immunization to relevant national reporting agencies as part of the process of post-marketing drug safety monitoring. In the US, the Vaccine Adverse Event Reporting System (VAERS) is co-sponsored by the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). Data from VAERS and other national and global reporting systems show very low rates of adverse events related to currently approved SARS-CoV-2 vaccines. Populations studies have supported the findings from adverse event reporting systems. The presentation, monitoring, and reporting of adverse events related to SARS-CoV-2 vaccines may have future applications in vaccine monitoring for several other potential pandemic zoonotic infections. This editorial aims to summarize the current understanding of adverse events from current COVID-19 vaccines from global adverse event reporting systems, rather than individual case reports or anecdotal reporting in the media.

Editorial: Global Initiatives Support the Use and Regulation of Digital Health Technology During the COVID-19 Pandemic.

The development and use of digital health technology have increased during the global COVID-19 pandemic. Artificial intelligence (AI)-powered digital tools have been increasingly used to diagnose and screen for SARS-CoV-2 infection. Digital technology, in the form of mobile phone applications (apps), has been adopted by several countries to track infected individuals as infection prevention and surveillance measures. Global best practice guidelines, technology approvals, and patient care models have only recently begun to catch up with the developments in digital technology. In 2021, the WHO published a global strategy on digital health (eHealth) and mobile health (mHealth) for 2020 to 2025. The US Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) now evaluates software as a medical device (SaMD) and software that is in a medical device (SiMD) through the International Medical Device Regulators Forum (IMDRF). This Editorial aims to discuss how the COVID-19 pandemic has driven global initiatives to support the use and regulation of digital health technology and the requirements for digital health evidence frameworks and new approaches to regulatory approvals.

Editorial: Multisystem Inflammatory Syndrome in Adults (MIS-A) and the Spectrum of COVID-19.

Recent studies on the pathogenesis and clinical spectrum of human disease following infection with the new human pathogen, SARS-CoV-2, have identified the varied presentations and sequelae of COVID-19. Acute 'cytokine storm' in severe COVID-19 results in multiorgan damage due to vascular hyperpermeability, edema, and hypercoagulation. The long-term consequences of infection from SARS-CoV-2 include long COVID. or post-COVID syndrome, and multisystem inflammatory syndrome in children (MIS-C). Several case reports of multisystem inflammatory syndrome in adults (MIS-A) have shown the presentation at more than four weeks after initial infection with SARS-CoV-2 in adults more than 21 years of age. In September 2021, a published systematic review of the literature identified 221 patients with MIS-A, representing the most comprehensive clinical study to date. MIS-A occurs in the post-acute COVID-19 period. The pathogenesis may involve a dysregulated antibody-mediated immune response, similar to MIS-C. Therefore, patients with MIS-A may respond to supportive therapies that control hyperinflammation. This Editorial aims to describe MIS-A and discuss COVID-19 as a spectrum of hyperinflammatory disease in terms of severity, extent, duration, and patient age.

Editorial: A Decline in Influenza During the COVID-19 Pandemic and the Emergence of Potential Epidemic and Pandemic Influenza Viruses.

There have been five viral pandemics in the past century, four were due to influenza, and the ongoing COVID-19 pandemic is due to SARS-CoV-2 infection. During the COVID-19 pandemic, there has been a 99% global reduction in the diagnosis of influenza. Also, from 2020, global mortality rates from influenza fell to record levels during the influenza seasons in the southern and northern hemispheres. However, as social restrictions become lifted and the winter season begins in the northern hemisphere, it is expected that influenza will re-emerge. The World Health Organization (WHO) FluNet surveillance platform provides global surveillance data on influenza, and the US Centers for Disease Control and Prevention (CDC) records national weekly infection rates. Both surveillance programs have identified zoonotic avian and swine influenza variants in humans. The WHO Pandemic Influenza Preparedness (PIP) Framework requires WHO Member States to share data on cases of emerging influenza viruses with pandemic potential in a regular and timely way. The WHO PIP Framework organizes the Global Influenza Surveillance and Response System (GISRS), a global network of public health laboratories developing candidate virus vaccines. This Editorial aims to present the reasons for concern regarding the emergence of pandemic influenza viruses driven by the social and public health responses to the COVID-19 pandemic and highlights the importance of global influenza surveillance at this time.

Editorial: Global Regulatory Initiatives Deliver Accelerated Approval of the First Bispecific Therapeutic Monoclonal Antibody for Advanced Non-Small Cell Lung Cancer (NSCLC).

The coronavirus disease 2019 (COVID-19) pandemic has affected the number of completed clinical trials, particularly in oncology. Between 80-85% of all lung cancers are non-small cell lung cancer (NSCLC), and of these, between 2-3% have an EGFR exon 20 insertion, which is associated with increased cell proliferation, metastasis, and a lack of response to chemotherapy and epidermal growth factor receptor (EGFR) inhibitors. Until this year, there were no available targeted therapies for advanced NSCLC with this genetic subtype. However, in May 2021, the US Food and Drug Administration (FDA) granted accelerated approval for amivantamab-vmjw (Rybrevant®), a bispecific monoclonal antibody, targeting activating and resistant EGFR and MET mutations and amplifications. This FDA approval was for adult patients with locally advanced metastatic NSCLC, with disease progression on or following platinum-based chemotherapy. The FDA also approved the Guardant360® companion diagnostic, a next-generation sequencing platform for circulating tumor DNA (ctDNA), which is a liquid biopsy assay. In 2019, Project Orbis was launched by the FDA Oncology Center of Excellence as a global collaborative review program to facilitate rapid global access for patients to innovative cancer therapies. This Editorial aims to highlight how global regulatory initiatives from the FDA have delivered accelerated approval of the first bispecific therapeutic monoclonal antibody, amivantamab-vmjw (Rybrevant®), and a companion diagnostic for patients with advanced NSCLC with an EGFR exon 20 insertion.

Editorial: Autoantibodies to Components of the Immune System, Including Type 1 Interferons, and the Risk of Severe COVID-19.

During the past two years, clinical studies have attempted to identify risk factors to predict clinical outcomes following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In July 2021, a study using a high-throughput technique detected autoantibodies to chemokines, cytokines, and complement components in patients with symptomatic coronavirus disease 2019 (COVID-19). In August 2021, a study identified pre-existing autoantibodies to type 1 interferons (IFNs) in 10% of patients with severe COVID-19 but not asymptomatic individuals. Autoantibodies may be the long-awaited markers of clinical risk for severe COVID-19 in patients with SARS-CoV-2 infection. This Editorial aims to present some recent findings of autoantibodies to components of the immune system, including type 1 IFNs, and the risk of severe COVID-19.

Editorial: First Full Regulatory Approval of a COVID-19 Vaccine, the BNT162b2 Pfizer-BioNTech Vaccine, and the Real-World Implications for Public Health Policy.

In the past 18 months, accelerated vaccine development to prevent or reduce the severity of coronavirus disease 2019 (COVID-19) has resulted in rapid global emergency regulatory approvals, including the US Food and Drug Administration (FDA) emergency use authorization (EUA) approvals. On August 23, 2021, the US FDA gave the first full regulatory approval for a COVID-19 vaccine and approved the Pfizer-BioNTech COVID-19 vaccine (Comirnaty) for individuals 16 years and older. In the US, there is a continued EUA for individuals aged 12-15 years of age. Also, the EUA includes the administration of a third or booster dose in immunocompromised individuals at increased risk for severe COVID-19. This Editorial aims to present an update on the first COVID-19 vaccine to receive full regulatory approval, the Pfizer-BioNTech vaccine, and the implications for real-world public health during the global COVID-19 pandemic and increasing concerns for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern.

Editorial: Reporting Clinical Trials with Important Modifications Due to Extenuating Circumstances, Including the COVID-19 Pandemic: CONSERVE 2021.

During 2020 and 2021, the COVID-19 pandemic has resulted in interruptions and cancellations of clinical trials and has delayed drug development in all areas except SARS-CoV-2 vaccine development. A further concern is the need to rapidly share anonymized datasets and improve opportunities to conduct randomized clinical trials (RCTs) in low-resource developing countries, particularly for oncology trials and for other infectious diseases. The Consolidated Standards of Reporting Trials (CONSORT) 2010 and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 currently guide the reporting of trial protocols and completed RCTs, respectively. Extenuating circumstances or unavoidable situations may occur that are beyond the control of study sponsors and investigators. On June 21, 2021, the CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance (CONSERVE) was published. The scope of CONSERVE 2021 includes modifications that have substantive implications for the feasibility, ethical conduct, scientific content, and study analysis. This Editorial aims to provide the background to CONSERVE 2021 and show how these guidelines may reduce the number of clinical trials currently being paused or discontinued due to the COVID-19 pandemic, particularly in poorly resourced and developing countries.

Editorial: Post-Exposure Prophylactic Neutralizing Monoclonal Antibodies to SARS-CoV-2 for Individuals at High Risk for COVID-19.

Regulatory authorities, including the US Food and Drug Administration (FDA), have accelerated diagnostic and therapeutic approvals during the coronavirus disease 2019 (COVID-19) pandemic. Accelerated clinical development and approvals have resulted in vaccine programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, some individuals remain at high risk for the progression of COVID-19. In the US, the FDA has given Emergency Use Authorization (EUA) for two neutralizing therapeutic monoclonal antibody 'cocktails,' casirivimab and imdevimab (REGEN-COV), bamlanivimab and etesevimab, and one monotherapy, bamlanivimab, for prophylactic post-exposure therapy in individuals at high risk of progressing to severe COVID-19. Preclinical and clinical studies showed consistent effectiveness of REGEN-COV against current variants of SARS-CoV-2. On 21st November 2020, the FDA approved an initial EUA for REGEN-COV to treat mild to moderate COVID-19 in adults and in children 12 years or older with exposure to SARS-CoV-2 at high risk for progression to severe COVID-19. On 30th July 2021, the FDA updated its EUA for REGEN-COV for emergency use as post-exposure prophylactic to prevent COVID-19 progression in adults and children aged 12 years or older. This Editorial aims to provide an update on accelerated regulatory authorization for post-exposure prophylactic neutralizing monoclonal antibodies to SARS-CoV-2 for individuals at high risk for COVID-19.