[A preview of COVID-19 vaccination and treatment]

Vaccination or recent exposure to infection with SARS-CoV-2 currently grants the vast majority of the population considerable immunity and thereby protection against severe disease. It is yet unknow how long this protection lasts. Continuous changes of the viral genotype and phenotype herein play an important role, in particular the variant-specific alterations of the spike protein. Protection by T-cell immunity seems to be more preserved in the event of changes in the virus as compared to antibody-mediated host defences. Furthermore, the continuous succession of virus variants also directly and indirectly affects the effectiveness of medical treatment. Regarding immune-modulating as well as anti-viral therapy, the viral characteristics of the circulating SARS-CoV-2 variant in combination with the level of host immunity will determine whether their use makes sense, and for which patients. The number of patients needed to treat to prevent a clinically negative outcome herein represents an important figure.

[Current and future therapeutic options for COVID-19]

The anti-inflammatory agents dexamethasone (corticosteroid), and tocilizumab and sarilumab (IL6-inhibitors) are effective in the treatment of late COVID-19. Other anti-inflammatory agents, like anakinra (IL1-inhibitor), baricitinib and tofacitinib (JAK-inhibitors) and lenzilumab (GM-CSF-inhibitor) have also shown positive results in late COVID-19. For the treatment of early COVID-19, the inhalation corticosteroid budesonide is regarded as an off-label treatment option. Virus-inhibitors, like remdesivir, molnupiravir and nirmatrelvir/ritonavir decrease the risk of hospitalization and the development of severe COVID-19 by patients with early symptoms. Monoclonal antibodies have shown limited or no efficacy against the omicron-variant of SARS-CoV-2. Fluvoxamine, l-arginine, AT-527 and ensovibep are considered as potential promising new therapies for the treatment of early COVID-19.

Vaccine effectiveness against COVID-19 related hospital admission in the Netherlands: A test-negative case-control study.

INTRODUCTION: Real-world vaccine effectiveness (VE) estimates are essential to identify potential groups at higher risk of break-through infections and to guide policy. We assessed the VE of COVID-19 vaccination against COVID-19 hospitalization, while adjusting and stratifying for patient characteristics. METHODS: We performed a test-negative case-control study in six Dutch hospitals. The study population consisted of adults eligible for COVID-19 vaccination hospitalized between May 1 and June 28, 2021 with respiratory symptoms. Cases were defined as patients who tested positive for SARS-CoV-2 by PCR during the first 48 h of admission or within 14 days prior to hospital admission. Controls were patients tested negative at admission and did not have a positive test during the 2 weeks prior to hospitalization. VE was calculated using multivariable logistic regression, adjusting for calendar week, sex, age, comorbidity and nursing home residency. Subgroup analysis was performed for age, sex and different comorbidities. Secondary endpoints were ICU-admission and mortality. RESULTS: 379 cases and 255 controls were included of whom 157 (18%) were vaccinated prior to admission. Five cases (1%) and 40 controls (16%) were fully vaccinated (VE: 93%; 95% CI: 81 - 98), and 40 cases (11%) and 70 controls (27%) were partially vaccinated (VE: 70%; 95% CI: 50-82). A strongly protective effect of vaccination was found in all comorbidity subgroups. No ICU-admission or mortality were reported among fully vaccinated cases. Of unvaccinated cases, mortality was 10% and 19% was admitted at the ICU. CONCLUSION: COVID-19 vaccination provides a strong protective effect against COVID-19 related hospital admission, in patients with and without comorbidity.

Remap-cap: Delivering research in the pandemic

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) pandemic is an unprecedented global health crisis. For hospitalised patients with Coronavirus Disease 2019 (COVID-19) mortality and morbidity is high. A case fatality rate of 49% for critically ill patients was reported in early studies. We urgently need effective treatments for these patients. In past pandemics, the clinical research response has largely failed. During the Influenza A(H1N1) pandemic, no randomised trials delivered results. Traditional randomised trials are not well suited for research in pandemics. They are robust, but lack the flexibility to adapt to changing circumstances and only investigate a single treatment against a control arm. Additionally, sample size calculations are almost impossible in new diseases. Adaptive platform trials, specifically REMAP-CAP, help overcome the challenges of pandemic research. We describe the key design principles of adaptive platform trials, the design of REMAP-CAP, and how this trial has delivered important results that contribute to the treatment of hospitalised and critically ill patients with COVID-19.

Digital means in the fight against COVID-19. Can a second wave be prevented? [Dutch]

Since the beginning of the Covid-19 epidemic, various digital tools have been developed, such as apps that can help fight SARS-CoV-2. With an app, GGDs can trace the contacts of people who have tested positive for SARS-CoV-2 more quickly and thus limit the further spread of the virus. Can a second wave be prevented with this?