Relapse in the first 8 weeks after onset of COVID-19 disease in outpatients: Viral reactivation or inflammatory rebound?

Buskermolen, Maaike; Paske, Karlijn Te; Beek, Janko van; Kortbeek, Titia; Götz, Hannelore M; Fanoy, Ewout; Feenstra, S.; Richardus, Jan Hendrik; Vollaard, Albert M.

doi:10.1016/j.jinf.2021.06.015

Cited by 9 publications

(10 citation statements)

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“…The median [Q1, Q3] symptom score at study enrollment was 10 points [6, 15]. Using both definitions of baseline, we assessed the frequency of symptom rebound (≥4 point increase in total symptom score) after initial improvement (Supplementary figure 2A, 2B).…”

Section: Resultsmentioning

confidence: 99%

“…However, many questions remain unanswered questions regarding this phenomenon. For example, the natural recovery from COVID-19 does not always progress in a linear fashion and clinical relapses can occur in the absence of antiviral treatment 5 , 6 . Case reports and case series may be subject to reporting bias and the incidence of viral and symptom rebound is difficult to determine as the denominator is challenging to estimate.…”

Section: Introductionmentioning

confidence: 99%

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Viral and Symptom Rebound in Untreated COVID-19 Infection

Deo

Choudhary

Moser

et al. 2022

Preprint

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Background: There are reports of viral RNA and symptom rebound in people with COVID-19 treated with nirmatrelvir/ritonavir. Since the natural course of viral and symptom trajectories of COVID-19 has not been well described, we evaluated the incidence of viral and symptom rebound in untreated outpatients with mild-moderate COVID-19. Methods: The study population included 568 participants enrolled in the ACTIV-2/A5401 platform trial who received placebo. Anterior nasal swabs were collected for SARS-CoV-2 RNA testing on days 0-14, 21 and 28. Participants recorded the severity of 13 targeted symptoms daily from day 0 to 28. Viral rebound was defined as ≥0.5 log10 viral RNA copies/mL increase and symptom rebound was defined as a 4-point total symptom score increase from baseline. Baseline was defined as study day 4 (primary analysis) or 8 days from symptom onset (secondary analysis). Findings: In both the primary and secondary analyses, 12% of participants had viral rebound. Viral rebounders were older than non-rebounders (median 54 vs 47 years, P=0.04). Symptom rebound occurred in 27% of participants after initial symptom improvement and in 10% of participants after initial symptom resolution. The combination of high-level viral rebound to ≥5.0 log10 RNA copies/mL and symptom rebound after initial improvement was observed in 1-2% of participants. Interpretation: Viral RNA rebound or symptom relapse in the absence of antiviral treatment is common, but the combination of high-level viral and symptom rebound is rare. Funding: This study was supported by the National Institute of Allergy and Infectious Diseases; ACTIV-2/A5401 ClinicalTrials.gov number NCT04518410.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Viral and Symptom Rebound in Untreated COVID-19 Infection

Deo

Choudhary

Moser

et al. 2022

Preprint

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“…We designed a new classical model based on traditional SEIR-typed to analyse the transmission of COVID-19 pandemic with consideration of possible relapse/reactivation and reinfection, which has been reported previously [29] , [30] , [31] , [32] , [41] , [42] , [46] , [47] . Moreover, our model considers two different modes of transmission, i.e., human-to-human or direct transmission and environment-to-human or indirect transmission [48] .…”

Section: Model Descriptionmentioning

confidence: 99%

“…SARS-CoV-2 reactivation seems improbable in mildly infected outpatients, especially those with no risk factors for severe infection. A relapse (which is of no or less infectiousness) observed during the first eight weeks of sickness implies that retest or isolation is unneeded [46] . Reinfection of SARS-CoV-2 is typically defined as clinical recurrence of COVID-19 followed by a positive PCR test in (

)90 days (on average) after commencement of the primary infection; it usually has reduced infectiousness compared to new infection [39] , [46] .…”

Section: Introductionmentioning

confidence: 99%

“…A relapse (which is of no or less infectiousness) observed during the first eight weeks of sickness implies that retest or isolation is unneeded [46] . Reinfection of SARS-CoV-2 is typically defined as clinical recurrence of COVID-19 followed by a positive PCR test in (

)90 days (on average) after commencement of the primary infection; it usually has reduced infectiousness compared to new infection [39] , [46] . Moreover, after a symptom-free interval and re-positive PCR outcomes, the motley of clinical recurrence of SARS-CoV-2 infection has not been researched vastly and may be rare in outpatients.…”

Section: Introductionmentioning

confidence: 99%

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