Albert Vollaard

Andes virus (ANDV) is unique among hantaviruses because person-to-person transmission ispossible. This raises questions on the relevance of post-exposure prophylaxis (PEP), particularlyfollowing high-risk household, healthcare-associated, or laboratory exposures, considering itshigh case fatality rate. Ribavirin has demonstrated antiviral activity against hantaviruses in vitroand in animal models, although clinical evidence supporting its use as treatment or PEP forANDV remains extremely limited. The available evidence consists primarily of cell cultureexperiments, Syrian hamster studies, pharmacokinetic and pharmacodynamic extrapolationsfrom other virusses, limited clinical data, and indirect clinical experience with other viralhemorrhagic fevers. This viewpoint summarizes the currently available evidence regardingribavirin as PEP after potential ANDV exposure. We discuss the knowledge gaps that may limitthe applicability of ribavirin PEP, to make informed decisions on the use of ribavirin in thesetting of PEP. Potential dosing strategies are visualized by modeling and simulation, andpotential dose and duration are discussed. Although the biologic rationale for ribavirin PEPappears compelling, the absence of controlled human studies and the potential toxicityassociated with ribavirin currently limit its role to highly selected exposure scenarios and useshortly after exposure.

Background: In recent decades, the number of immunocompromised patients (ICPs) has increased significantly. ICPs have an impaired immune system, making them susceptible to complicated infections. To protect them from infections, ICPs are eligible to receive several medically indicated vaccines. To obtain insight into the uptake of these medically indicated vaccines, we determined the coverage of these vaccines in ICPs. Methods: This observational cohort study was conducted at the University Medical Centre Utrecht, the Netherlands, from September 2021 to April 2022. All adult ICPs admitted for COVID-19 were asked to complete a questionnaire on their vaccination history (pneumococcal, herpes zoster, human papillomavirus vaccination, influenza, and COVID-19 vaccines) and history of vaccine-preventable infections. In addition, patients’ vaccination history was reviewed in medical files. Results: A total of 115 patients completed the questionnaire and were included. Although all patients had an indication for pneumococcal vaccination, only 22 received it (19%). Coverage for herpes zoster was low (1%, 1/106 eligible patients). Coverage for human papillomavirus vaccination (HPV) was also low (40%, two out of five eligible patients). In contrast, 92% of patients received vaccination against SARS-CoV-2, and 77% of patients received seasonal influenza vaccination. Conclusions: Although coverage for influenza and COVID-19 vaccination was high in ICPs, coverage for other medically indicated vaccines was low. Identifying which factors contributed to high COVID-19 and influenza vaccine uptake can help to improve vaccination rates for the other recommended vaccines. Clear guidelines for clinicians and the removal of organizational obstacles are needed to improve vaccination coverage.

Influenza infection increases the risk of cardiovascular complications and mortality in patients with heart disease. In patients with coronary artery disease influenza vaccination has been shown to reduce cardiovascular mortality, but high-quality evidence was missing. New trial data from a RCT in patients shortly after myocardial infarction has confirmed the significant reduction of the risk of major adverse cardiovascular events (MACE) and cardiovascular death after influenza vaccination. Also in patients with heart failure the first published RCT in heart failure shows a clinical benefit of influenza vaccination versus placebo during the influenza season, confirming preceding observational studies. Meta-analyses from the study data estimate that after influenza vaccination a risk reduction of MACE of at least 25% is possible in patients with heart disease. The current underutilization of influenza vaccines in heart patients should be addressed because influenza vaccination has proven to be an effective and safe instrument for secondary prevention.

Immunosuppressive therapy increases the risk of pneumococcal disease. This risk can be mitigated by pneumococcal vaccination. The objective of this study was to investigate the immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13), followed by the 23-valent pneumococcal polysaccharide vaccine (PPSV23), in adults with and without immunosuppressive therapy. We performed a prospective cohort study among adults using conventional immunomodulators (cIM), biological immunomodulators (bIM), combination therapy, and controls during 12 months. The primary outcome was seroprotection, defined as the proportion of patients with a postimmunization IgG concentration of ≥1.3 µg/mL for at least 70% (17/24) of the serotypes of PCV13 + PPSV23. We included 214 participants. For all 24 vaccine serotypes, IgG levels increased significantly in both treatment subgroups and controls, with peak seroprotection rates of 44% (combination therapy), 58% (cIM), 57% (bIM), and 82% (controls). By month 12, seroprotection had decreased to 24%, 48%, 39%, and 63%, respectively. Although pneumococcal vaccination with PCV13 + PPSV23 was immunogenic in all treatment groups, impaired vaccination responses were observed in patients using immunosuppressive medication. Apart from the obvious recommendation to administer vaccines before such medication is started, alternative vaccination strategies, such as additional PCV13 doses or higher-valent pneumococcal vaccines, should be investigated.