Microbiology & Infectious Diseases
The publication of this
infographic was funded by an
unrestricted educational grant
from Shionogi Inc. (U.S.).
The Evolving COVID-19 Landscape:
Role of Post-Exposure Prophylaxis
THE PERSISTENT BURDEN OF COVID-19
IN VULNERABLE POPULATIONS
THE UNMET NEED FOR PROPHYLAXIS
THE PERSISTENT BURDEN OF COVID-19
IN VULNERABLE POPULATIONS
Hospitalizations due to COVID-19 have declined, but SARS-CoV-2 transmission remains high in high-exposure settings and disproportionately affects high-risk populations.1-3
In vulnerable patients, SARS-CoV-2 infection increases hospitalizations, disrupts chronic care, and worsens health outcomes.4,5
COVID-19-related hospitalization rates are higher in high-risk populations.6
Interactive quiz
OMICRON SUBLINEAGES ARE MORE TRANSMISSIBLE AND HARDER TO CONTAIN
Infection characteristics of SARS-CoV-2 Omicron:13-16
High mutation load:
32 spike protein mutations
Short incubation period:
3 days
High household SAR:
21–54%
Omicron spreads more effectively within households, even among vaccinated individuals.17
Interactive Question
Alpha
Omicron
Delta
The SAR of SARS-CoV-2 variants differs.17
Which of these variants has the highest SAR?
CLINICAL RATIONALE
FOR EARLY INTERVENTION
Reduced hospitalization burden
Decreased viral load
Reduced severe outcomes in LTCF residents
Oral antivirals offer meaningful clinical benefit when used early.18,19
Key benefits of early intervention:
•
•
•
CLINICAL CONSIDERATIONS FOR PEP USING EMERGING ANTIVIRALS
Early PEP with oral antivirals aims to protect vulnerable populations and reduce COVID-19 transmission in high-risk settings.20-22
Click to explore the clinical profile of oral antivirals being investigated for PEP
Critical window for early PEP intervention*,†,14,23
0
1
2
3
4
5
Day 5+:
Established infection
Day 0: Exposure
Day 1-3:
Viral replication begins
Day 1-3:
PEP initiation
Day 3-5:
Symptom onset
*Based on SARS-CoV-2 Omicron | †Optimal timing may vary depending on the antiviral agent
Interrupt transmission chains
Prevent hospitalization spikes
Preserve continuity of chronic care
•
•
•
Early PEP in households and LTCFs could:19,23
CONCLUSION
The persistent burden of COVID-19 in vulnerable populations, coupled with the high transmissibility of Omicron sublineages and significant SAR, underscores the critical need for effective PEP strategies.6,13-17
Key takeaways
References
Support: The publication of this infographic was funded by an unrestricted educational grant from Shionogi Inc. (U.S.).
Keywords: Burden, COVID-19, Omicron, post-exposure prophylaxis, SARS-CoV-2, immunocompromised patients, older adults, individuals with comorbidities.
Original Citation: Microbiol Infect Dis AMJ. 2025; https://doi.org/10.33590/microbiolinfectdisam/NQJL4678
COVID-19-related hospitalization rates are higher in high-risk populations6
General population (1x baseline)
Immunocompromised adults ≥65 years without underlying conditions (1.3x baseline risk)
Immunocompromised population (5.4x baseline risk)
Immunocompromised adults ≥65 with ≥3 underlying conditions (9.3x baseline risk)
COVID-19-related hospitalization rate (%)
0
5
10
15
20
25
2.3%
12.5%
3%
21.3%
Question
Which of the following respiratory infections had the highest 30-day hospitalization rate in 2022–2023?
RSV
Influenza
COVID-19
Select the correct answer
The Burden of COVID-19 Remains
Higher Than That of Other Respiratory Infections
The risk of severe outcomes for SARS-CoV-2 infection exceeds that of influenza and RSV, especially for older adults, patients who are immunocompromised, and those with comorbidities.7,8
COVID-19
RSV
Influenza
Thirty-day hospitalization and mortality
rates in 2022–20238
RSV
COVID-19
Influenza
14.4%
15.9%
17.5%
30-day hospitalization rate
30-day mortality rate
0.7%
0.7%
1.0%
THE UNMET NEED FOR PROPHYLAXIS
THE PERSISTENT BURDEN OF COVID-19
IN VULNERABLE POPULATIONS
THE UNMET NEED FOR PROPHYLAXIS
Limited effectiveness of vaccines in high-risk populations
Although an essential first line of defense, vaccines do not fully protect certain high-risk groups.9-11
Vaccine protection wanes over time
A 2022 study found waning of protection from vaccines against pre-Omicron variants, and lower vaccine protection against Omicron.12
Patients who are immunocompromised
Individuals with multiple comorbidities
Individuals with underlying health conditions
Patients who are immunocompromised
Around 20% of patients who are immunocompromised
do not develop protective antibodies after ≥3 COVID-19 vaccinations.9
Individuals with multiple comorbidities
Patients with multiple comorbidities have a two-times increased risk of severe breakthrough infection despite vaccination.10
People living in LTCFs
People living in LTCFs
LTCF residents have an increased risk of SARS-CoV-2 infection and COVID-19-related mortality.11
Omicron
Omicron has a higher SAR than both Alpha and Delta17
Omicron 42.7%
Alpha
36.4%
Delta
29.7%
Delta
Alpha
Efficacy metrics21,22
Broad activity against multiple variants Antiviral effect
Reduced viral load
•
•
•
Fewer COVID-19 symptoms in clinical trials
Improved early recovery in clinical trials Lower household transmission
•
•
•
Clinical outcomes22,23
Well-tolerated
No new concerns in published Phase III data Convenient dosing
•
•
•
Safety21-23
Emerging oral antivirals offer promising avenues to reduce the burden of hospitalization, viral load, and transmission, providing crucial protection where vaccines may offer limited efficacy.21-23
Implementing timely PEP interventions is essential to mitigate the ongoing impact of COVID-19 and protect those at highest risk.19-23
References
1. Choi T et al. Open Forum Infect Dis. 2025;12(3):ofaf115.
2. Sumsuzzman DM et al. BMC Infect Dis. 2025;25(1):215.
3. Singson JRC et al. MMWR Morb Mortal Wkly Rep. 2022;71(27):878-84.
4. Li Y et al. J Chemother. 2025;DOI:10.1080/1120009X.2025.2458377.
5. Hanson HA et al. SN Compr Clin Med. 2023;5(1):144.
6. Fang C et al. Infect Dis Ther. 2025;14(6):1343-67.
7. Xing Y, Bahl A. J Clin Med. 2025;14(14):4894.
8. Bajema KL et al. JAMA Intern Med. 2025;185(3):324-34.
9. Pearce FA et al. Lancet Rheumatol. 2023;5(8):e461-73.
10. Meister T et al. Sci Rep. 2023;13(1):8531.
11. Rolland Y et al. BMJ Public Health. 2025;3(1):e002156.
12. Chemaitelly H, Abu-Raddad LJ. Lancet. 2022;399(10327):771-3.
13. Ma W et al. Genomics Proteomics Bioinformatics. 2022;20(1):60-9.
14. Del Águila-Mejía J et al. Emerg Infect Dis. 2022;28(6):1224-8.
15. Song JS et al. Emerg Infect Dis. 2022;28(3):756-9.
16. Lyngse FP et al. Nat Commun. 2022;13(1):5760.
17. Madewell ZJ et al. JAMA Netw Open. 2022;5(4):e229317.
18. Vegivinti CTR et al. BMC Infect Dis. 2022;22(1):107.
19. Ma BH et al. JAMA Netw Open. 2023;6(4):e2310887.
20. Mitjà O, Clotet B. Lancet Glob Health. 2020;8(5):e639-40.
21. Hammond J et al. N Engl J Med. 2024;391(3):224-34.
22. Ohmagari N et al. Influenza Other Respir Viruses. 2024;18(6):e13338.
23. Hayden FG et al. Abstract 200. CROI, 9-12 March, 2025.
Abbreviations:
LTCF: long-term care facility; PEP: post-exposure prophylaxis; RSV: respiratory syncytial virus; SAR: secondary attack rate.
Individuals with multiple comorbidities
Patients who are immunocompromised