Current recommendation for high-risk patients!

The wave of colds is already well underway. The number of coronavirus infections is rising steadily again – and with it the number of infected people from potential risk groups. In Switzerland, antiviral treatment with nirmatrelvir/ritonavir is recommended for patients with a low to moderately increased risk of severe COVID-19 and for high-risk patients [1].

The virus responsible for COVID-19, SARS-CoV-2, has continuously evolved since the beginning of the pandemic and has given rise to variants such as Alpha, Beta, Delta and most recently Omikron [2]. Omikron was first identified in South Africa in November 2021 and classified as a variant of concern (VOC) by the World Health Organization (WHO) due to its increased transmissibility and ability to evade neutralizing antibodies induced by vaccination or natural infection with the wild-type virus [3]. The Omikron variant has evolved into several sublines with additional mutations in the spike gene and elsewhere in the genome, resulting in several successive waves of Omikron sublines around the world [4,5]. In Switzerland, Omikron XBB is the predominant variant (around 90% of confirmed infections, as of June 18, 2023) [5], explains Prof. Marta Boffito, member of the Royal College of Physicians, MBA, London [6].

The lasting risks of COVID-19

Although almost 70% of the world’s population has been vaccinated against COVID-19 at least once [7] and immunization due to previous infection and/or vaccination still provides some protection against severe COVID-19 disease, the vaccination loses its protective effect over time and especially against the currently circulating Omicron XBB sublines [8]. Although bivalent vaccines have a higher protective effect than previous monovalent substances, they are already showing signs of a waning effect [9]. In addition, several risk factors such as advanced age and immunosuppression despite vaccination can lead to an increased incidence of severe COVID-19 disease [10].

SARS-CoV-2, similar to influenza, RSV and other coronaviruses, usually reaches its peak of disease activity between November and April [11,12]. In contrast, the risk of mortality in hospital is 1.5 times higher in patients with a SARS-CoV-2 Omicron variant compared to influenza (HR: 1.54; 95% CI: 1.18-2.01; p=0.002) [13]. An increased incidence of severe COVID-19 disease is also recorded in high-risk patients [10]. For example, the COVID-19-related death rate increases with age and is 360 times higher for over 85-year-olds than for 20-29-year-olds [14]. The Federal Office of Public Health (FOPH) also lists certain forms of chronic diseases such as obesity, diabetes, high blood pressure and chronic lung and respiratory diseases as risk factors [15]. For example, an increased risk of hospitalization due to COVID-19 was observed in patients with high blood pressure despite triple vaccination [16].

With antiviral drugs against COVID-19

In Switzerland, antiviral treatment with nirmatrelvir/ritonavir (^Paxlovid®) is therefore recommended for patients with a low to moderately increased risk of severe COVID-19 disease progression and for high-risk patients [1]. Treatment should be started as soon as possible after a positive COVID-19 test in order to effectively reduce the risk of a severe course of the disease. Early therapy is essential for the efficacy of nirmatrelvir/ritonavir, as the course of a SARS-CoV-2 infection starts with a high viral load at the beginning of the infection and can later lead to the formation of thrombi and organ dysfunction due to an excessive immune response [17,18]. A randomized controlled pivotal study (Evaluation of Protease Inhibitor for COVID-19 in High-Risk Patients, EPIC-HR) showed that nirmatrelvir/ritonavir reduced the relative risk of COVID-19-related hospitalization or death from any cause by 88.9% compared to placebo when treatment was started three days after symptom onset and by 87.8% when treatment was started five days after symptom onset [19].

How is Nirmatrelvir/Ritonavir used?

As a rule, the prescribed dose is 300 mg nirmatrelvir and 100 mg ritonavir every 12 hours for five consecutive days, but this should be adjusted for moderate renal insufficiency [20]. Furthermore, a careful review of drug interactions and contraindications is essential before prescribing and can be supported by digital tools such as the Liverpool COVID-19 Drug Interaction Checker [20,21].

Source: Pfizer

Literature:

Swiss Society for Infectiology (SSI). Recommendations on the early use of Covid-19 therapies and prophylaxis prepared by the Swiss Society of Infectious Diseases (SSI), version February 6, 2023. www.bag.admin.ch/bag/de/home/krankheiten/ausbrueche-epidemien-pandemien/aktuelle-ausbrueche-epidemien/novel-cov/information-fuer-die-aerzteschaft/covid19_vo_2.html. Last call: 24.05.2023.
Yale Medicine. Omicron, Delta, Alpha, and More: What To Know About the Coronavirus Variants. 3 February 2023. www.yalemedicine.org/news/covid-19-variants-of-concern-omicronlast. Last call: 10.07.2023.
Madhi SA, et al: Population Immunity and Covid-19 Severity with Omicron Variant in South Africa. N Engl J Med 2022, Apr 7; 386(14): 1314-1326.
Dhawan M, et al: Omicron variant (B.1.1.529) and its sublineages: What do we know so far amid the emergence of recombinant variants of SARS-CoV-2? Biomed Pharmacother 2022 Oct; 154: 113522.
Federal Office of Public Health (FOPH). COVID-19 Switzerland. Information on the current situation, as of June 27, 2023. Epidemiological course, Switzerland and Liechtenstein. Virus variants. www.covid19.admin.ch/en/epidemiologic/virus-variants. Last call: 04.07.2023.
Boffito M: Paxlovid Pfizer Media Roundtable. 14.09.2023.
Our world in data: Coronavirus (COVID 19) Vaccinations. Available at: https://ourworldindata.org/covid-vaccinations,(last accessed: 28.08.2023).
Link Gelles R, et al: Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID 19 Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions. VISION Network, September 2022 April 2023, MMWR Morb Mortal Wkly Rep, 2023, 72(21): 579-588.
Lin DY, et al: Effectiveness of Bivalent Boosters against Severe Omicron Infection. N Engl J Med 2023; 388(8): 764-766.
Centers for Disease Control and Prevention (CDC): Factors That Affect Your Risk of Getting Very Sick from COVID 19. as of May 11, 2023. Available at: www.cdc.gov/coronavirus/2019-ncov/your-health/risks-getting-very-sick.html. Last call: 11.05.2023.
Nichols GL, et al: Coronavirus seasonality, respiratory infections and weather BMC Infect Dis 2021, 21(1): 1101.
Wiemken TL, et al: Seasonal trends in COVID 19 cases, hospitalizations, and mortality in the United States and Europe Sci Rep 2023. 13(1): 3886.
Portmann L, et al: Hospital Outcomes of Community Acquired SARS CoV 2 Omicron Variant Infection Compared With Influenza Infection in Switzerland. JAMA Netw Open, 2023. 6(2): e2255599.
Centers for Disease Control and Prevention (CDC). Risk for COVID 19 Infection, Hospitalization, and Death By Age Group. As of May 30, 2023. Available at: https://archive.cdc.gov/#/details?q=&start=0&rows=10&url=https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-age.html. Last call: 04.07.2023.
Federal Office of Public Health (FOPH). Categories of particularly vulnerable persons. As of August 10, 2022. Available at: www.bag.admin.ch/bag/de/home/krankheiten/ausbrueche-epidemien-pandemien/aktuelle-ausbrueche-epidemien/novel-cov/information-fuer-die-aerzteschaft/covid-19-impfung.html. Last call: 28.08.2023.
Ebinger JE, et al: Hypertension and Excess Risk for Severe COVID 19 Illness Despite Booster Vaccination. Hypertension 2022; 79(10): e132-e134.
Siddiqi HK, et al: COVID 19 illness in native and immunosuppressed states: A clinical therapeutic staging proposal. J Heart Lung Transplant 2020; 39(5): 405-407.
Cevik M, et al: Virology, transmission, and pathogenesis of SARS CoV 2. Bmj 2020; 371: m3862.
Hammond J, et al: Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid 19 N Engl J Med, 2022; 386(15): 1397-1408.
^PAXLOVID® (nirmatrelvir [PF-07321332] and ritonavir): current information for healthcare professionals at www.swissmedicinfo.ch.
Liverpool COVID-19 Drug Interactions. Available at: https://covid19-druginteractions.org. Last call: 28.08.2023.