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Rapid response to:


Sixty seconds on . . . covid rebound

BMJ 2022; 377 doi: (Published 30 May 2022) Cite this as: BMJ 2022;377:o1365

Rapid Response:

Covid-19 Pandemic, Reinfection, Reactivation and Covid-19 Rebound: Efficacy of Covid-19 Pharmaceutical and Non-Pharmaceutical Interventions; The Imperative to Guard Against Interventional Precosity in Downing Guards

Dear Editor

The recent ‘Communication’ in the BMJ is as instructive as it is revealing [1]. The COVID-19 Pandemic has been replete with Controversies, Uncertainties, Politics-Science Conflicts, Infodemic and ‘Rapidly Transmuting and Evolving Realities/ Specifics’ as ‘Information in a Flux’ or ‘Difficult Work in Progress’. Increasingly, too many ‘Issues’ appear not to be known with certainty concerning COVID-19 Pandemic re: Origin, Nomenclature/ Taxonomy of the Disease and Aetiologic Agents (Variants and Sub-variants), Susceptibility/ Vulnerability, Transmission, Manifestation, Treatment, Outcomes and Prevention among others. These were ventilated in previous ‘Communications’ [2-13].

The ‘COVID-19 Rebound’ [14] throws a ‘New Spanner in the Difficult Works’! The ‘COVID-19 Rebound’ is ‘Recurrence of symptoms 2 to 8 days after initial recovery or new positive for COVID-19 Testing after previously testing negative’ as conveyed in the recent Health Alert Network (HAN) and Health Advisory of the Center for Disease Control and Prevention (CDC) dated 24th May 2022. This is now an ‘Evolving COVID-19 Conversation’ in the face of extant ‘COVID-19 Pandemic Interventions’. Generically, there are ‘COVID-19 Pharmaceutical Interventions’ (Drugs, Convalescent Plasma/ Serum, Monoclonal Antibodies and Vaccines, etc) and ‘COVID-19 Non-Pharmaceutical Interventions’ (Lockdowns/ Shutdowns, Shelter-in-Place, Face Mask Use, Social Distancing, No Mass Gatherings, Hand Washing/ Hygiene and Respiratory Hygiene, etc). The ‘Non-Pharmaceutical Interventions (NPIs)’ are the ‘COVID-19 Interventions’ that are acclaimed to be efficacious: The ‘Interventions that Work’! Not so for the ‘COVID-19 Pharmaceutical Interventions’ which are ventilated further vide infra!

For ‘COVID-19 Vaccines’, there have been ‘Issues’ related to the following: Speed of Vaccine Research and Development/ Clinical Trials and Population Diversity/ Disparities, Populace Vaccine Uptake/ Vaccine Hesitancy, Seroconversion and Duration/ Protection, Dosage Regimen and Boosters, ‘2nd Dose Uncertainties’, Definition of ‘Full Vaccination’ and Vaccine Efficacy with ‘Evolving SARS-CoV-2 Variants and Sub-variants’ among others. Indeed, several ‘COVID-19 Cases’ have recently been recorded among ‘Vaccinated Persons’ with the ‘Recommended Dosage Regimen’ including ‘Vaccine Booster Doses’. This raises the ‘Determinant Question’: Are the ‘COVID-19 Vaccines’ effective? The argument of reduced ‘Hospitalizations’ and ‘Deaths’ among ‘Vaccinated Persons’ is attractive but ‘Infection’ in such persons is equally troubling.

And now: the ‘COVID-19 Pharmaceuticals’ with the Antiviral Paxlovid (Nirmatrelvir/ Ritonavir) as a case-in-point? The CDC Health Advisory is instructive [14]. Paxlovid is ‘Recommended for early stage treatment of mild to moderate COVID-19 among persons at high risk for progression to severe disease’. ‘COVID-19 Cases’ are now documented to manifest the ‘COVID-19 Rebound’ after completing the ‘Recommended Paxlovid Regimen’ irrespective of ‘Vaccination Status’ and are ‘Infectious’15 requiring ‘Re-Isolation’ for at least 5 ‘Full Days’ and ‘Masking’ for at least ’10 Full Days’ from the ‘Restart’ of symptoms or New Positive Test (See the recent CDC Health Advisory) [14]. It is not clear whether ‘Genomic Sequencing’ was done for the ‘SARS-CoV-2 Variants’ in the ‘COVID-19 Rebound’ to establish the confirmed reality of the ‘Possibilities’: Reinfection, Reactivation or Rebound. Again this raises yet another ‘Determinant Question’: Are the ‘COVID-19 Antivirals’ effective? The argument of reduced ‘Hospitalizations’ and ‘Deaths’ among ‘Treated Persons’ is again attractive but, equally too, ‘Infection’ and ‘Infectiousness’ in such persons is quite bothersome for ‘Efficacious COVID-19 Interventions’.

Given the ‘Uncertainties’ with the ‘Efficacies’ of the ‘COVID-19 Pharmaceutical Interventions’, it becomes imperative to stick tenaciously with the ‘Interventions that Work’: the NPIs! For the ‘Global Fight’ against the ‘CIVID-19 Pandemic’, the world must guard against ‘Interventional Precocity’ in ‘Downing Guards’ concerning the NPIs. The ‘COVID-19 Pharmaceutical Interventions’ are not yet the envisioned ‘Interventional Magic Bullets’.

This ‘Communication’ is a modest ‘Contribution’ to the ‘Evolving COVID-19 Rebound Conversation’ and a ‘Clarion Call’, as an imperative, to uphold the NPIs with the continually evolving ‘COVID-19 Pandemic Specifics’ which remain ‘Information in a Flux’ and ‘Difficult Work in Progress’.

1. Mahase E. Sixty seconds on ………. .covid rebound. BMJ 2022; 377:o1365
2. Godlee F. COVID-19: Weathering the storm. BMJ 2020; 368:m1199 of 26th March 2020
3. Eregie C.O. COVID-19 Pandemic: The difficult unresolved increasing challenges in weathering the storm. of 31st March 2020
4. Eregie C.O. COVID-19 Pandemic: Still on the difficult unresolved increasing challenges in weathering the storm. of 2nd April 2020
5. 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
6. Eregie C.O. COVID-19 Pandemic: Further perspectives on the difficult unresolved increasing challenges in weathering the storm. of 5th April 2020
7. Eregie C.O. COVID-19 Pandemic: The daunting challenges of assuring sustainable benefits from weathering the storm. of 8th April 2020
8. Eregie CO. COVID-19 Pandemic and the Value of Antibodies Testing: Still More Matters in the Works. of 14th August 2020
9. Mahase E. Covid-19: Vaccine brands can be mixed in ‘extremely rare occasions’ says Public Health England. BMJ 2021; 372:n12
10. 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
11. Eregie CO. ‘COVID-19 Pandemic, beyond the ‘Vaccines Marathon Finish Line’ and ‘Post-Vaccines Approval Programmatic Haze’: The evolving ‘2nd Dose Uncertainties’; still more unfolding ‘Matters in the Work’. of 27th January 2021
12. Eregie CO. ‘COVID-19 Pandemic, COVID-19 Vaccines and ‘2nd Dose Uncertainties’: Still unresolved evolving matters’. of 8th February 2021
13. 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
14. CDC. Covid-19 rebound after paxlovid treatment.
15. Charness M, Gupta K, Stack G, Strymish J, Adams E, Lindy D, Mohi H, Ho D. Rapid relapse of symptomatic omicron SARS-CoV-2 infection following early suppression with nirmatrelvir/ ritonavir. 13th May 2022. PREPRINT (Version 2) available at Research Square (

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

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