Meningococcal meningitis in Spain in the Horizon 2030: A position paper.

Meningococcal meningitis (MM) and invasive meningococcal disease remain a major public health problem that generates enormous public alarm. It is caused by Neisseria meningitidis, a Gram-negative diplococcus with an enormous capacity for acute and rapidly progressive disease, both episodic and epidemic in nature, with early diagnosis and treatment playing a major role. It occurs at any age, but is most common in children under 5 years of age followed by adolescents. Although most cases occur in healthy people, the incidence is higher in certain risk groups. Despite advances in reducing the incidence, it is estimated that in 2017 there were around 5 million new cases of MM worldwide, causing approximately 290,000 deaths and a cumulative loss of about 20,000,000 years of healthy life. In Spain, in the 2021/22 season, 108 microbiologically confirmed cases of MM were reported, corresponding to an incidence rate of 0.23 cases per 100,000 inhabitants. This is a curable and, above all, vaccine-preventable disease, for which the World Health Organisation has drawn up a roadmap with the aim of reducing mortality and sequelae by 2030. For all these reasons, the Illustrious Official College of Physicians of Madrid (ICOMEM) and the Medical Associations of 8 other provinces of Spain, have prepared this opinion document on the situation of MM in Spain and the resources and preparation for the fight against it in our country. The COVID-19 and Emerging Pathogens Committee of ICOMEM has invited experts in the field to participate in the elaboration of this document.

Respiratory syncytial virus: A new era.

Respiratory syncytial virus (RSV) is a major public health problem that has undergone significant changes in recent years. First of all, it has become easier to diagnose with highly reliable and rapidly available confirmatory tests. This has led to a better understanding of its epidemiology and RSV has gone from being a disease of the pediatric age group, severe only in infants and immunosuppressed children, to being a common disease in people of all ages, particularly important in patients of advanced age or with immunosuppressive diseases. Recent therapeutic and prophylactic advances, both with long-lasting monoclonal antibodies and vaccines, are another reason for satisfaction. For these reasons, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has considered it pertinent to review this subject in the light of new knowledge and new resources for dealing with this infection. We have formulated a series of questions that we believe will be of interest not only to members of the College but also to any non-expert in this subject, with a particular focus on the situation of RSV infection in Spain.

COVID-19: On the threshold of the fifth year. The situation in Spain.

Despite having emerged from pandemic status, the incidence of COVID-19 episodes has recently increased in Spain, including pediatric cases and admissions to Intensive Care Units. Several recombinant variants are circulating among us, particularly XBB arising from two Omicron BA.2 sublineages with mutations in the genes encoding the spicule proteins that could increase binding to the ACE2 receptor and be more prone to immune escape. Faced with these, 3 pharmaceutical companies have developed vaccines adapted to the XBB.1.5 sublineage that are already available for administration in our setting with risks that should not be different from those of previous mRNA vaccines and with clearly favorable benefit/risk ratios. They should be applied to patients with potential for poor COVID-19 evolution and to collectives that have a particular relationship of proximity with them. Their application should be understood not only from a perspective of individual convenience but also from that of collective responsibility. The most convenient seems to be a simultaneous immunization of COVID-19 and influenza in our environment. In the therapeutic aspect, there is little to expect right now from antisera, but the already known antiviral drugs are still available and indicated, although their efficacy will have to be reevaluated due to their impact on populations that are mostly immunized and with a better prognosis than in the past. In our opinion, it is necessary to continue to make a reasonable and timely use of masks and other non-pharmacological means of protection.

Tuberculosis in Spain: An opinion paper.

This document is the result of the deliberations of the Committee on Emerging Pathogens and COVID-19 of the Illustrious Official College of Physicians of Madrid (ICOMEM) regarding the current situation of tuberculosis, particularly in Spain. We have reviewed aspects such as the evolution of its incidence, the populations currently most exposed and the health care circuits for the care of these patients in Spain. We have also discussed latent tuberculosis, the reality of extrapulmonary disease in the XXI century and the means available in daily practice for the diagnosis of both latent and active forms. The contribution of molecular biology, which has changed the perspective of this disease, was another topic of discussion. The paper tries to put into perspective both the classical drugs and their resistance figures and the availability and indications of the new ones. In addition, the reality of direct observation in the administration of antituberculosis drugs has been discussed. All this revolution is making it possible to shorten the treatment time for tuberculosis, a subject that has also been reviewed. If everything is done well, the risk of relapse of tuberculosis is small but it exists. On the other hand, many special situations have been discussed in this paper, such as tuberculosis in pediatric age and tuberculosis as a cause for concern in surgery and intensive care. The status of the BCG vaccine and its present indications as well as the future of new vaccines to achieve the old dream of eradicating this disease have been discussed. Finally, the ethical and medicolegal implications of this disease are not a minor issue and our situation in this regard has been reviewed.

Advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in Spain. How and when is it justified to maintain it?

We address the advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in the current epidemiological situation in Spain and after the declaration of the World Health Organization on May 5, 2023 of the end of COVID-19 as public health emergency. We advocate for prudence and flexibility, respecting the individual decision to wear a mask and emphasizing the need for its use when symptoms suggestive of a respiratory infection appear, in situations of special vulnerability (such as immunosuppression), or when caring for patients with those infections. At present, given the observed low risk of severe COVID-19 and the low transmission of other respiratory infections, we believe that it is disproportionate to maintain the mandatory use of masks in a general way in health centers and nursing homes. However, this could change depending on the results of epidemiological surveillance and it would be necessary to reconsider returning to the obligation in periods with a high incidence of respiratory infections.

Sexually transmitted infections in Spain: Current status.

Sexually Transmitted Infections (STI) are a major public health problem. The problems inherent to their diagnosis, treatment and prevention have to do not only with their nature, but also with organizational issues and overlapping competencies of the different health authorities in Spain. The real situation of STI in Spain, at present, is poorly known. For this reason, the Scientific Committee on COVID and Emerging Pathogens of the Illustrious Official College of Physicians of Madrid (ICOMEM) has formulated a series of questions on this subject which were distributed, not only among the members of the Committee, but also among experts outside it. The central health authorities provide very high and increasing figures for gonococcal infection, syphilis, Chlamydia trachomatis infection and lymphogranuloma venereum (LGV). Both HIV infection and Monkeypox are two important STI caused by viruses in our environment, to which it should be added, mainly, Herpes simplex virus (HSV) and Human papillomavirus (HPV) infections. Emerging microorganisms such as Mycoplasma genitalium pose not only pathogenic challenges but also therapeutic problems, as in the case of N. gonohrroeae. The pathways that patients with suspected STI follow until they are adequately diagnosed and treated are not well known in Spain. Experts understand that this problem is fundamentally managed in public health institutions, and that Primary Care and Hospital Emergency Services, together with some institutions that deal monographically with this problem, are the recipients of most of these patients. One of the most serious difficulties of STI lies in the availability of the microbiological tests necessary for their diagnosis, particularly in this era of outsourcing of microbiology services. Added to this is the increased cost of implementing the latest generation of molecular techniques and the difficulties of transporting samples. It is clear that STI are not diseases to which the entire population is equally exposed and it is necessary to have a better knowledge of the risk groups where to focus the necessary interventions adapted to their characteristics. It should not be forgotten that STI are also a problem in the pediatric age group and that their presence can be a marker of sexual abuse with all that this implies in terms of health care and medicolegal activity. Finally, STI are infections that are associated with a high cost of care for which we have very little information. The possibility of expanding the automatic performance of laboratory tests for STI surveillance through laboratory routines is encountering ethical and legal problems that are not always easy to solve. Spain has created a ministerial area of specific attention to STI and there are plans to improve the diagnosis, treatment and prevention of these problems, but we still lack the necessary evidence on their impact. We cannot forget that these are diseases that transcend the individual and constitute a Public Health problem.

Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.

Herpes zoster infection (HZ) is an important public health problem due to its high incidence and frequent complications, especially post-herpetic neuropathy . The incidence of HZ increases with age and is more frequent in immunocompromised patients. It is estimated that at least 60,000 people develop HZ each year in Spain. The usual forms of HZ are so clinically characteristic that they do not usually require microbiological confirmation, which is reserved for cases without cutaneous manifestations or with atypical presentation. There are currently two vaccines approved by the regulatory agencies and marketed in Spain to prevent the onset of HZ and its complications. The first (Zostavax®) was marketed by the company MSD and licensed in Europe in 2006 and is a live attenuated virus vaccine that is administered in a single dose, while the second (Shingrix®) is a recombinant vaccine, marketed in 2017 and requires two doses. While the former cannot be administered to immunocompromised persons, the latter can be prescribed to any group of adults. The criteria for the indication and financing of these vaccines have not been uniform in the various autonomous communities of Spain. These and other aspects of HZ have been discussed by a group of experts from the Illustrious Official College of Physicians of Madrid (ICOMEM) whose criteria and opinions are included in this paper.

Insights for COVID-19 in 2023.

Predictions for a near end of the pandemic by the World Health Organization should be interpreted with caution. Current evidence indicates that the efficacy of a fourth dose of classical mRNA vaccines (BT162b2 or mRNA-1273) is low and short-lived in preventing SARS-CoV-2 infection in its predominant variant (Omicron). However, its efficacy is high against severe symptomatic infection, hospitalization and death. The new vaccines being introduced are bivalent and active against the Omicron variants. Potential new vaccines to be introduced in the coming year include a vaccine based on a recombinant protein that emulates the receptor binding domain of the Spike protein under development by the Spanish company Hipra, as well as vaccines for nasal or oral administration. Available information suggests that vaccines against COVID-19 can be administered in association with influenza vaccination without particular complications. New drugs against COVID-19, both antiviral and anti-inflammatory, are under investigation, but this does not seem to be the case with monoclonal antibodies. The indication to use masks in some circumstances will be maintained next year in view of the accumulation of scientific data on their efficacy. Finally, the long COVID or Post-COVID syndrome may continue to affect a very high proportion of patients who have had the disease, requiring combined diagnostic and therapeutic resources.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España / Consensus statement on the use of alemtuzumab in daily clinical practice in Spain

Introducción: Alemtuzumab es un fármaco de alta eficacia aprobado por la Agencia Europea de Medicamentos como tratamiento modificador de la enfermedad en pacientes con esclerosis múltiple remitente recurrente.ObjetivoElaborar un documento de consenso sobre el manejo de alemtuzumab en la práctica clínica habitual, que sea de aplicación en el ámbito español.DesarrolloUn grupo de expertos en esclerosis múltiple revisó las publicaciones disponibles hasta diciembre de 2017, de tratamiento con alemtuzumab y esclerosis múltiple. Se incluyeron trabajos sobre eficacia, efectividad y seguridad, despistaje de infecciones y vacunación, administración y monitorización. La propuesta inicial de recomendaciones fue desarrollada por un grupo coordinador con base en la evidencia disponible y en su experiencia clínica. El proceso de consenso se llevó a cabo en 2 etapas; se estableció como porcentaje inicial de acuerdo grupal el 80%. El documento final con todas las recomendaciones acordadas por el grupo de trabajo se sometió a revisión externa y los comentarios recibidos fueron considerados por el grupo coordinador.ConclusionesEl documento aportado pretende ser una herramienta útil para facilitar el manejo del fármaco en condiciones de práctica clínica habitual. (AU)

Introduction: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis.ObjectiveA consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain.DevelopmentA group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group.ConclusionThe present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice. (AU)

Monkeypox in humans: a new outbreak.

Infection caused by Monkeypox Virus (MPVX) has small rodents as its natural reservoir and both monkeys and humans are occasional hosts. The causative agent is an Orthopoxvirus (MPVX) that was isolated in monkeys in 1958 and proved capable of passing to humans in 1970. It remained contained in Africa, causing isolated episodes of infection, until 2003 when an outbreak occurred in the United States following importation of animals from that continent. Since then, anecdotal cases have continued to be reported outside Africa, usually very clearly linked to travelers to those countries, but in May 2022, a broad outbreak of this disease has begun, now affecting several continents, with the emergence of human cases of MPVX (H-MPVX) infection mainly among Men that have Sex with Men (MSM). The disease has an incubation time ranging from 5 to 15 days and is characterized by the presence of pustules, fever, malaise and headache. The presence of significant regional lymphadenopathy is a differential feature with episodes of classical smallpox. Proctitis and pharyngitis, with minimal skin lesions, may be another form of presentation. Diagnosis can be confirmed by PCR testing of lesions or by demonstration of MPVX in other body fluids or tissues, although in the appropriate epidemiologic setting the clinical picture is highly suggestive of the disease. Effective drug treatment has been developed as part of programs to protect against potential bioterrorist agents and smallpox vaccinees are known to have high protection against monkeypox. New vaccines are available, but neither the drugs nor the vaccines are yet freely available on the market. The prognosis of the disease appears, at least in adults in developed countries, to be good, with very low mortality figures and much less aggressive behavior than that described in classical smallpox. Isolation measures, essential for the control of the outbreak, have been published by the health authorities.

Lessons from COVID-19 for future disasters: an opinion paper.

A "Pandemic/Disaster Law" is needed to condense and organize the current dispersed and multiple legislation. The State must exercise a single power and command appropriate to each situation, with national validity. The production of plans for the use of land and real estate as potential centers for health care, shelter or refuge is recommended. There should be specific disaster plans at least for Primary Health Care, Hospitals and Socio-sanitary Centers. The guarantee of the maintenance of communication and supply routes is essential, as well as the guarantee of the autochthonous production of basic goods. The pandemic has highlighted the need to redefine the training plans for physicians who, in their different specialties, have to undertake reforms that allow a more versatile and transversal training. National research must have plans to be able to respond quickly to questions posed by the various crises, using all the nation's resources and in particular, all the data and capabilities of the health sector. Contingency plans must consider ethical aspects, and meet the needs of patients and families with a humanized approach. In circumstances of catastrophe, conflicts increase and require a bioethical response that allows the best decisions to be made, with the utmost respect for people's values. Rapid, efficient and truthful communication systems must be contained in a special project for this sector in critic circumstances. Finally, we believe that the creation of National Coordination Centers for major disasters and Public Health can contribute to better face the crises of the future.

COVID-19: Some unresolved issues.

Two years after the COVID-19 pandemic, many uncertainties persist about the causal agent, the disease and its future. This document contains the reflection of the COVID-19 working group of the Official College of Physicians of Madrid (ICOMEM) in relation to some questions that remain unresolved. The document includes considerations on the origin of the virus, the current indication for diagnostic tests, the value of severity scores in the onset of the disease and the added risk posed by hypertension or dementia. We also discuss the possibility of deducing viral behavior from the examination of the structure of the complete viral genome, the future of some drug associations and the current role of therapeutic resources such as corticosteroids or extracorporeal oxygenation (ECMO). We review the scarce existing information on the reality of COVID 19 in Africa, the uncertainties about the future of the pandemic and the status of vaccines, and the data and uncertainties about the long-term pulmonary sequelae of those who suffered severe pneumonia.

COVID in Pediatric Age: an opinion paper.

The incidence of COVID in pediatrics was underestimated during the first months of the pandemic due to the oligosymptomatic nature of the infection in many children and the scarcity of diagnostic tests applied to this population. It is now accepted that children are infected and transmit the disease in the same way as adults. On the contrary, children have less severe and less lethal COVID, probably due to a lower maturity of the child's immune system, a lower number of ACE2 receptors and the lower presence of comorbidities in this population group. The development of a multisystemic inflammatory syndrome after SARS-CoV-2 infection in children, despite its rarity, is a very serious condition that frequently requires intensive care. Other less severe post-COVID manifestations have been described in children but are not yet well defined. COVID has had and continues to have a significant psychological impact on the children themselves, on their caregivers and on the exacerbation of pre-existing psychiatric conditions. We apply adult therapeutic principles to children but with very low levels of evidence. Information on the tolerability of the available medications in this population group is still scarce. The mortality of COVID in children is very low and generally affects children with significant comorbidities. There are, at present, three vaccines licensed for pediatric use which are compatible with all other vaccines applicable to children. In these circumstances, there has been much speculation about the indication for vaccination in the pediatric age group, but given its good tolerance, there are clinical and ethical reasons that, in our opinion, justify it.

Pharmacological treatment of COVID-19: an opinion paper.

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.

Booster or additional vaccination doses in patients vaccinated against COVID-19.

Several health organizations, mainly in Western countries, have recently authorized the use of a booster dose of the COVID-19 vaccine for patients previously vaccinated with mRNA vaccines, with criteria that do not always coincide. The COVID Scientific Committee of the Illustrious College of Physicians of Madrid (ICOMEM) has received and asked several questions about this situation, to which the group has tried to give answers, after deliberation and consensus. The efficacy of the vaccines administered so far is beyond doubt and they have managed to reduce, fundamentally, the severe forms of the disease. The duration of this protection is not well known, is different in different individuals and for different variants of the virus and is not easily predictable with laboratory tests. Data on the real impact of a supplementary or "booster" dose in the scientific literature are scarce for the moment and its application in large populations such as those in the state of Israel may be associated with a decrease in the risk of new and severe episodes in the short observation period available. We also lack sufficient data on the safety and potential adverse effects of these supplementary doses and we do not know the ideal time to administer them in different situations. In this state of affairs, it seems prudent to administer supplemental doses to those exposed to a higher risk, such as immunocompromised individuals and the elderly. On the other hand, we consider that this is not the time to accelerate, on the spur of the moment, a massive administration of a third dose to other population groups that are less exposed and at lower risk, without waiting for adequate scientific information, which will undoubtedly arrive gradually. We do not believe that this position is incompatible with the practical and ethical warnings made by the World Health Organization in this respect.

Persistence and viability of SARS-CoV-2 in primary infection and reinfections.

Since the beginning of the SARS-CoV-2 epidemic, virus isolation in the infected patient was only possible for a short period of time and it was striking that this occurred constantly and did not provide guidance on the clinical course. This fact led to confusion about the efficacy of some of the drugs initially used, which seemed to have a high efficiency in viral clearance and proved ineffective in modifying the course of the disease. The immune response also did not prove to be definitive in terms of evolution, although most of the patients with very mild disease had a weak or no antibody response, and the opposite was true for the most severe patients. With whatever the antibody response, few cases have been re-infected after a first infection and generally, those that have, have not reproduced a spectrum of disease similar to the first infection. Among those re-infected, a large number have been asymptomatic or with very few symptoms, others have had a moderate picture and very few have had a poor evolution. Despite this dynamic of rapid viral clearance, laboratory tests were still able to generate positive results in the recovery of genomic sequences and this occurred in patients who were already symptom-free, in others who were still ill and in those who were very seriously ill. There was also no good correlate. For this reason and with the perspective of this year and the half of pandemic, we compiled what the literature leaves us in these aspects and anticipating that, as always in biology, there are cases that jump the limits of the general behavior of the dynamics of infection in general.

Actions and attitudes on the immunized patients against SARS-CoV-2.

The access to COVID vaccines by millions of human beings and their high level of protection against the disease, both in its mild and severe forms, together with a plausible decrease in the transmission of the infection from vaccinated patients, has prompted a series of questions from the members of the College of Physicians of Madrid (ICOMEM) and the society. The ICOMEM Scientific Committee on this subject has tried to answer these questions after discussion and consensus among its members. The main answers can be summarized as follows: The occurrence of new SARS-CoV-2 infections in both vaccinated and previously infected patients is very low, in the observation time we already have. When breakthrough infections do occur, they are usually asymptomatic or mild and, purportedly, should have a lower capacity for transmission to other persons. Vaccinated subjects who have contact with a SARS-CoV-2 infected patient can avoid quarantine as long as they are asymptomatic, although this decision depends on variables such as age, occupation, circulating variants, degree of contact and time since vaccination. In countries with a high proportion of the population vaccinated, it is already suggested that fully vaccinated persons could avoid the use of masks and social distancing in most circumstances. Systematic use of diagnostic tests to assess the immune response or the degree of protection against reinfection after natural infection or vaccination is discouraged, since their practical consequences are not known at this time. The existing information precludes any precision regarding a possible need for future revaccination. This Committee considers that when mass vaccination of health care workers and the general population is achieved, SARS-CoV-2 screening tests could be avoided at least in outpatient care and in the case of exploratory procedures that do not require hospitalization.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain. / Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

New variants of SARS-CoV-2.

The emergence and spread of new variants of SARS-CoV-2 has produced enormous interest due to their possible implication in the improved transmissibility of the virus, their consequences in the individual evolution of the infection, as well as in the possible escape from the immunity generated by the current vaccines. The variants that attract most attention are those of public health concern, including B.1.1.7 (UK), P.1 (Brazilian) and B.1.351 (South African). This list is extended by the variants of interest that emerge and are expanding in certain countries but are found sporadically in others, such as B.1.427 and B.1.429 (Californians) or B.1.617 (Indian). Whole genome sequencing or strategies specifically targeting the spicule gene are used in the microbiology laboratories for characterization and detection. The number of infected individuals, the sanitary situation of each country, epidemiological measures and vaccination strategies influence its dispersion and new variants are expected to emerge. This emergence can only be avoided today by increasing the vaccinated population in all countries and by not relaxing epidemiological containment measures. It is not excluded that in the future it will be necessary to revaccinate against new variants.