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Immunity and infectivity in covid-19

BMJ 2022; 378 doi: (Published 01 July 2022) Cite this as: BMJ 2022;378:e061402

Rapid Response:

COVID-19 pandemic, immunity and infectivity: evolving facts support the imperative for sustained compliance with non-pharmaceutical interventions

Dear Editor

For ‘COVID-19 Pandemic Specifics’, the ‘FACTS’ are continuously unfolding disposing ‘Difficult Work In Progress’. The recent ‘Communication’ on ‘Immunity and Infectivity’ in ‘COVID-19’ is revealing and instructive.[1] ‘Infectiousness’ and ‘Risk of Transmission’ are greatest just before and immediately after the onset of symptoms while ‘Infectivity’ and ‘Viral Load’ decrease therefrom.[2,3] After 10 days, mild to moderate cases are very unlikely to be infectious.[4,5] The ‘Guidelines’ keep changing but remain the source of information to guide ‘COVID-19 Pandemic Control’[6-8]; ‘Self-Isolation’ is no longer a UK legal requirement for a ‘COVID-19 Case’ but recommended.[8] The ‘COVID-19 Pandemic Specifics’ are rapidly transmuting and confusing compliance with ‘Precautionary Measures’.[9-16] Healthworkers may ‘Self-Isolate’ until two Negative Lateral Flow Tests taken 24 hours apart starting from 5 days after the initial Positive Test. If still positive, testing continues till 10 days after which ‘Infectiousness’ is unlikely and the person may return to work if fit medically.[17]

‘Infectiousness’ is influenced by ‘Host Factors’, ‘Contact Factors’, ‘Viral Factors’, ‘Nature of Exposure’ and ‘Behavioural Factors’ including ‘Super Spreader Events’ where 20% of infected individuals are possibly responsible for 80% of all infections.[1] With the transmuting and unfolding ‘COVID-19 Specifics’ and the unsettled ‘Issues’ with ‘COVID-19 Pharmaceuticals’ (Vaccines-Antivirals), together with the ‘Immunity-Infectivity Issues’, compliance additionally with ‘Non-Pharmaceutical Interventions (NPIs)’ remains the promising option.[18]

More facts are disposed concerning ‘Infectivity’-‘Infectiousness’ and their ‘Surrogate Markers’. Presence of ‘Culturable Virus’ (‘Infectivity’) may not necessarily imply ‘Infectiousness’[19] and ‘Positive Culture’ is more likely after 10 days in ‘Severe Disease’.[20,21] The ‘PCR Test’ detects ‘Non-viable Virus’ (‘Infectivity’) but not ‘Infectiousness’ and ‘Persistent Positivity’ prolongs unnecessary hospitalizations, isolations and stress on health facilities.[22] Samples from the Lower Respiratory Tract remain ‘PCR Test Positive’ for much longer and be considered in evaluating ‘Infectivity’-‘Infectiousness’.[23] The ‘Number of Cycles to achieve Positive Result’ (‘Cycle Threshold (CT)’) is also important in evaluating ‘Infectivity’-‘Infectiousness’! Low Cycle Threshold (CT) (< 25) implies High Viral Load and Strong Positivity and ‘High Infectiousness’ while High CT (> 35) reflects Low Viral Load, Weak Positivity and ‘Low Infectiousness’.[24] Lateral Flow Devices (LFDs) detect ‘Wall Protein Antigens’ indicating ‘Active Replication’ and ‘Infectiousness’ but are less sensitive than the PCR though more ‘Rapid Test’.[25]

It is also suggested that ‘Immunity’ is higher in ‘Infected Persons’ who are also ‘Vaccinated’ than in ‘Infected Persons’ without subsequent ‘Vaccination’.[26] With ‘Reinfection’, there may be ‘Asymptomatic PCR Positivity’ and disease may be mild to severe raising ‘Issues’ of ‘Vaccine Efficacy’. So, compliance with ‘COVID-19 Pandemic Precautionary Measures’ remains vital. Other ‘Surrogate Markers’ of ‘SARS-CoV-2 Infection’ are Antibodies and T-Cells and how these reflect ‘Immunity’, ‘Infectivity’ and ‘Infectiousness’ remain ‘Issues for Conversation’ in ‘COVID-19 Pandemic’ as ‘Presence of Antibodies’ is not ‘Proof of Immunity’.[1] ‘Immunity’ from ‘COVID-19’ is not life-long[27] and ‘Different Strains’ of Coronaviruses are responsible for ‘Seasonal Coronavirus Infections’ which change periodically every 2-4 years.[28] ‘Reinfection’ with the same strain results in ‘Complete Immunity’ that may last a year while it is only ‘Partial Immunity’ with a different strain.[28] The presence of ‘Neutralizing Antibodies’ is most predictive of ‘Protection’ and most ‘Infected Persons’ (Over 90%) have these even though it may be absent, low but stronger and longer-lasting with Severe Disease.[29] We should recall the ‘Vaccination-Immunization-Protection Transformation Complex’.

Vaccination presumably protects against all strains but is reduced against Omicron Variant and ‘Immunity’ wanes over time. The UK Joint Committee on Vaccination and Immunization is, therefore, recommending a ‘4th Vaccine Dose’ (Possibly a 2nd Booster Dose as applicable).[30] This is a ‘Subtle Programmatic Pointer’ to the ‘Queried Vaccine Efficacy Reality’. In the circumstance, STRICT COMPLIANCE with the NPIs is it; the NPIs are the ‘COVID-19 Pandemic Interventions’ that work.

1. Johnston C, Hughes H, Lingard S, Hailey S, Healy B. Immunity and Infectivity in covid-19. BMJ 2022; 378:e061402
2. World Health Organization. Transmission of SARS-CoV-2: implications for infection prevention precautions: scientific brief. 2020.
3. He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med 2020; 26:672-5
4. Walsh KA, Spillane S, Comber L, et al. The duration of infectiousness of individuals infected with SARS-CoV-2. J Infect 2020; 81:847-56
5. Cevik M, Tate M, Lloyd O, et al. SARS-CoV-2, SARS-CoV-1 and MERS-CoV viral load dynamics, duration of viral shedding and infectiousness: a living systematic review and meta-analysis. Lancet 2020; doi:10.2139/ssrn.3677918
6. Public Health Wales. Infection prevention and control measures for SARS-CoV-2 (COVID-19) in health and care settings-Wales. 2022.
7. Park M, Pawliuk C, Nguyen T, et al. Determining the period of communicability of SARS-CoV-2: a rapid review of the literature. 2020. MedRxiv 2020. 20163873, doi:10.1101/2020.07.28.20163873
8. NHS UK. What to do if you have coronavirus (COVID-19) or symptoms of COVID-19. 2022.
9. Godlee F. COVID-19: Weathering the storm. BMJ 2020; 368:m1199 of 26th March 2020
10. Eregie C.O. COVID-19 Pandemic: The difficult unresolved increasing challenges in weathering the storm. of 31st March 2020
11. Kickbusch I, Leung GM, Bhutta ZA, Matsoso MP, Ihekweazu C, Abbasi K. Covid-19: how a virus is turning the world upside down. BMJ 2020; 369:m1336 of 3rd April 2020
12. Eregie C.O. COVID-19 Pandemic: Further perspectives on the difficult unresolved increasing challenges in weathering the storm. of 5th April 2020
13. Mahase E. Covid-19: Vaccine brands can be mixed in ‘extremely rare occasions’ says Public Health England. BMJ 2021; 372:n12
14. Eregie CO. ‘COVID-19 Pandemic, beyond the ‘Vaccines Marathon Finish Line’ and ‘Post-Vaccine Approval Programmatic Haze’: The Evolving ‘2nd Dose Uncertainties’. of 24th January 2021
15. Eregie C.O. COVID-19 Pandemic, COVID-19 Vaccines and successful vaccination programmes: a further clarion call to observe research governance-related best practices and a critical look at preprints. of 23rd February 2022
16. Eregie C.O. COVID-19 Pandemic, COVID-19 Vaccines and Boosters: More Unresolved Evolving Matters in the Works. of 17th December 2021
17. Welsh Government. Self-isolation: guidance for people with COVID-19 and their contacts. 2022.
18. World Health Organization. Advice on the use of masks in the context of COVID-19: interim guidance, 6 April 2020. 2020.
19. Abe T, Ikeda T, Tokuda Y, et al. A patient infected with SARS-CoV-2 over 100 days. QJM 2021; 114:47-9
20. Van Kampen JJA, van de Vijver DAMC, Fraaij PLA, et al. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (CIVD-19). Nat Commun 2021; 12:267
21. Folgueira MD, Luczkowiak J, Lasala F, Perez-Rivilla A, Delgado R. Persistent SARS-CoV-2 replication in severe COVID-19. MedRxiv (2020)
22. Gombar S, Chang M, Hogan CA, et al. Persistent detection of SARS-CoV-2 RNA in patients and healthcare workers with COVID-19. J Clin Virol 2020; 129:104477
23. Lui G, Ling L, Lai CK, et al. Viral dynamics of SARS-CoV-2 across a spectrum of disease severity in COVID-19. J Infect 2020; 81:318-56
24. LaScola B, Le Bideau M, Andreani J, et al. Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards. Eur J Clin Microbiol Infect Dis 2020; 39:1059-61
25. Pickering S, Batra P, Merrick B, et al. Comparative performance of SARS-CoV-2 lateral flow antigen tests and association with detection of infectious virus in clinical specimens: a single-centre laboratory evaluation study. Lancet Microbe 2021; 2:e461-71
26. Hall V, Foulkes S, Insalata F, et al. SIREN Study Group. Protection against SARS-CoV-2 after Covid-19 vaccination and previous infection. N Engl J Med 2022; 386:1207-20
27. Kellam P, Barclay W. The dynamics oh humoral immune responses following infection with SARS-CoV-2 and other coronaviruses: A rapid review. Rev Med Virol 2020; 101:791-7
28. Reed SE. The behavior of recent isolates of human respiratory coronavirus in vitro and in voluteers: evidence of heterogeneity among 229E-related strains. J Med Virol 1984; 13:179-92
29. Ibarrondo FJ, Fulcher JA, Goodman-Meza D, et al. Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild Covid-19. N Engl J Med 2020; 383:1085--7
30. Andrews N, Stowe J, Kirsebom F, et al. Covid-19 vaccine effectiveness against the omicron (B,1.1.529) variant. N Engl J Med 2022; 386:1532-46

Professor Charles Osayande Eregie,
MBBS, FWACP, FMCPaed, FRCPCH (UK), Cert. ORT (Oxford), MSc (Religious Education),
Professor of Child Health and Neonatology, University of Benin, Benin City, Nigeria.
Consultant Paediatrician and Neonatologist, University of Benin Teaching Hospital, Benin City, Nigeria.
UNICEF-Trained BFHI Master Trainer,
ICDC-Trained in Code Implementation,
*Technical Expert/ Consultant on the FMOH-UNICEF-NAFDAC Code Implementation Project in Nigeria,
*No Competing Interests.

Competing interests: No competing interests

23 July 2022
Institute of Child Health, College of Medical Sciences, University of Benin, Benin City, Nigeria
PMB 1154, Benin City, 300001, Edo State, Nigeria