Sunday, June 26, 2022

EID Journal: Early SARS-CoV-2 Reinfections within 60 Days and Implications for Retesting Policies


Whenever a new infectious disease like COVID-19  emerges, initial assumptions must be made based on similar viruses (and epidemics) of the past, in order to quickly formulate case definitions, testing policies, and infection control measures.   

Since COVID was identified as a novel coronavirus, much of what had been learned from the 2003 SARS epidemic (see SARS And Remembrance) was assumed to be true.

For that reason, asymptomatic transmission, aerosol or `airborne' transmission, and extra-pulmonary manifestations (blot clots, neurological manifestations, cardiac problems, etc.) from the virus were thought unlikely.  

Similarly, durable post-infection acquired immunity - which was seen with SARS - was thought probable, making reinfections unlikely and `herd immunity' an achievable goal. 

Despite initial resistance, one-by-one we've seen these initial assumptions fall, as the virus has proved to be far more complex, and challenging, than the original SARS virus. 

EID Journal: Asymptomatic or Presymptomatic Transmission Of SARS-CoV-2

Nature Med. Review: Extrapulmonary manifestations of COVID-19

During the first two years of COVID, reinfection - while it was well documented - was fairly rare. But after antigenically highly divergent Omicron variant(s) emerged in late 2021, reinfections - and vaccine breakthrough infections - have soared. 

As a result, some of the assumptions about reinfections and the duration of immunity following infection (and vaccination) that worked reasonably well with the first 3 COVID variants (D614G, Alpha & Delta) may no longer apply.

Case in point, the ECDC defines a Suspected COVID Reinfection as:

Positive PCR or rapid antigen test (RAT) sample ≥60 days following:
  • Previous positive PCR
  • Previous positive RAT
  • Previous positive serology (anti-spike IgG Ab)
Many countries extend this up to 6 months, assuming that any `COVID' illness that occurs in the interim is most likely a `relapse', not a reinfection.  As a result, reinfections are likely badly undercounted, and many people may erroneously assume that their illness `couldn't be COVID' so soon after a prior infection. 

All of which brings us to the following EID Journal Research Letter, which describes multiple documented cases of reinfection (by different lab-confirmed variants) well within the 60-day window. 

I've only posted some excerpts, so follow the link to read it in its entirety.  I'll have a postscript after the break. 

Research Letter
Early SARS-CoV-2 Reinfections within 60 Days and Implications for Retesting Policies

Louis Nevejan , Lize Cuypers, Lies Laenen, Liselotte Van Loo, François Vermeulen, Elke Wollants, Ignace Van Hecke, Stefanie Desmet, Katrien Lagrou, Piet Maes, and Emmanuel André 


Illustrated by a clinical case supplemented by epidemiologic data, early reinfections with SARS-CoV-2 Omicron BA.1 after infection with Delta variant, and reinfection with Omicron BA.2 after Omicron BA.1 infection, can occur within 60 days, especially in young, unvaccinated persons. The case definition of reinfection, which influences retesting policies, should be reconsidered.

The sequential emergence of SARS-CoV-2 variants of concern (VOCs), characterized by an antigenic drift and higher transmissibility, has been observed in countries around the world at least 3 times during the past 13 months (1). Although the SARS-CoV-2 Delta variant showed a limited antigenic diversity with previous VOCs, Omicron differs more notably from other VOCs than any previous VOC did at the time it emerged (K. Van der Straten et al., unpub. data, Link).
The resulting decrease of antibody efficacy in both convalescent and vaccinees’ serum samples drives the high number of reinfection and vaccine breakthrough cases observed with Omicron compared with observations made during previous waves (2,3).

To date, reinfections with SARS-CoV-2 are defined by the European Centre for Disease Prevention and Control as a positive PCR or rapid antigen test >60 days after previous positive PCR, rapid antigen test, or serologic test (4). This definition has influenced testing strategies in several countries, and many countries consider a person protected for 180 days after an initial positive test result (5). We suggest that this reinfection definition should be revised.

To illustrate our point, we report a case of an immunocompetent unvaccinated 10-year-old boy with no noteworthy medical history who tested positive for SARS-CoV-2 Delta variant (>7.0 log copies/mL, sublineage AY.43) on December 3, 2021, concomitant with an outbreak at the patient’s school. The patient’s brother and mother, both vaccinated, were infected as well. All 3 persons experienced mild COVID-19 symptoms. Because of a sports-related trauma, the patient was admitted for surgery on January 11, 2022.
Preprocedural SARS-CoV-2 screening detected a strong positive result (5.1 log copies/mL) with Omicron BA.1 variant, only 39 days after the patient’s infection with Delta. The patient remained pauci-symptomatic. High-risk contact screening of the patient’s brother detected a low viral load; the mother tested SARS-CoV-2–negative (Appendix Table).


Previous retrospective cohort studies (2) showing a prolonged maintenance of protection against reinfection should be questioned after the emergence of Omicron. Our data confirm that early Omicron BA.1 reinfection (<60 days) after Delta infection and BA.2 reinfection after BA.1 infection can occur, especially in young, unvaccinated persons. In older patient groups, unvaccinated persons and persons who had received basic vaccination but no booster might be more vulnerable to reinfections than patients who received a first booster vaccine. Data from Denmark (M. Stegger et al., unpub. data, Link) suggest reinfection usually results in mild disease not requiring hospitalization, as demonstrated by the case we report here.

The occurrence of a full viral replacement in a matter of weeks will continue to affect the duration and efficacy of immunity in the future. For this reason, in cases of sustained variant circulation, indications for retesting persons after a previous SARS-CoV-2 infection within 180 days are limited. However, in cases of cocirculation or switch of VOC with antigenic drift within this period, this minimum retesting interval should be omitted to adequately detect SARS-CoV-2 reinfections.

This article was preprinted at Link.

Mr. Nevejan is a trainee in clinical biology at the Department of Laboratory Medicine of University Hospitals Leuven. His current research interest is the field of epidemiology and medical microbiology.

With BA.4 and BA.5 raising the bar on immune escape, reinfections - and `breakthrough' infections - with COVID are likely to become far more prevalent in the months ahead (see NEJM: Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5).

While the emphasis on testing has decreased across the board over the past 6 months, it is important that people (including clinicians) realize that reinfections can occur literally within weeks of a previous bout of COVID. 

And it is worth noting that with concerns over the cumulative effects of repeated COVID infection rising (see Outcomes of SARS-CoV-2 Reinfection), another assumption - that repeated COVID infections lessen the impact of the virus - may be teetering as well.