COVID-19 reinfection can occur after varying times and with more severe disease

Simon Collins, HIV i-Base

Several cases of reinfection with COVID-19 have now been reported, including several cases that were published this week following peer review.

All were supported as reinfection by phylogenetic analysis, some occurred shortly after the first infection, and some reported more serious disease.

The first case, reported in August, was a 33-year-old Hong Kong resident who was diagnosed and hosptialised with COVID-19 in March 2020, and discharged after 17 days. On 15 August, more than 140 days since the first infection, he tested positive a second time while asymptomatic due to travel-related screening (returning to Hong Kong from the UK). Although hospitalised, he remained asymptomitic. Phylogenetic analysis showed that the two viral genomes had different clade/lineages. [1]

Another paper from the same group reported that serum neutralising antibody was detected during the first infection but not at presentation of the second. During reinfection, neutralising antibody and high avidity IgG were found within eight days of hospitalisation, but an IgM response was not detected. [2]

A second case, reported on 31 August and just published in Lancet Infectious Diseases, was of a 25 year old man in Nevada who was infected in March, recovered in April and then experienced a second infected in May 2020. Both infections were symptomatic, but the second led to more severe disease requiring hospitalisation and oxygen support. Sequence analysis showed the viruses were unlikely to be linked. [3]

A third case also reported reinfections within a short time. This was a 42 year old man who was diagnosed with symptomatic COVID-19 on 21 March 2020 that resolved with out-patient management within 10 days. He remained healthy for 51 days before developing fever, cough and other symptoms on 24 May that were significantly worse that the first infection. Genetic sequencing of the partial first virus showed distinct differences to the second infection and included a high-confidence variation. [4]

Finally, a fourth case, reported this week in CID, was an 89 year old immunecompromised women treated with B-cell-depleting therapy for Waldenström’s macroglobulinemia. She was also diagnosed with SARS-CoV-2 and discharged after five days. 

Then, 59 days from the first symptoms, two days after a second course of chemotherapy, she was diagnosed with SARS-CoV-2 for a second time. Unfortunately this became progressively severe and the patient died after two weeks. Phylogenetic analysis of the two strains showed differences in ten nucleoside positions that was more likely to be from a second infection rather than developing from prolonged shedding. [5]

comment

An online database tracks both suspected and confirmed cases of people who experience COVID-19 more than once. Links are included to detailed reports.

Currently it list 30 confirmed cases (including 1 death) from 14 countries and more than 2000 suspected cases (including 25 deaths). [6, 7]

A later review in CID discuses the clinical implications of reinfection, especially in the context on vaccines against COVID-19. [8]

References

1. To KK Hung IF Ip JD et al. COVID-19 re-infection by a phylogenetically distinct SARS- coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis, ciaa1275. DOI: 10.1093/cid/ciaa1275. (25 August 2020).
   https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1275/5897019
2. To KKW et al. Serum antibody profile of a patient with COVID-19 reinfection. Clinical Infectious Diseases, ciaa1368, DOI: 10.1093/cid/ciaa1368. (23 September 2020.
   https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1368/5910650
3. Tillett RSJ et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet infectious Diseases. DOI: 10.1016/S1473-3099(20)30764-7. (12 October 2020).
   https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30764-7/fulltext
4. Larson D et al. A case of early re-infection with SARS-CoV-2. Clinical Infectious Diseases ciaa1436 https://doi.org/10.1093/cid/ciaa1436. (19 September 2020).
   https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1436/5908892
5. Mulder M et al. Reinfection of SARS-CoV-2 in an immunocompromised patient: a case report. Clinical Infectious Diseases, ciaa1538. DOI: 10.1093/cid/ciaa1538. (09 October 2020).
   https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1538/5920950
6. BNO news. Confirmed cases of COVID-19 reinfection.
   https://bnonews.com/index.php/2020/08/covid-19-reinfection-tracker
7. BNO news. Suspected cases of COVID-19 reinfection.
   https://bnonews.com/index.php/reinfection-tracker-suspected-cases
8. Cohen JI et al, Reinfection with SARS-CoV-2: Implications for Vaccines, Clinical Infectious Diseases, ciaa1866, DOI: 10.1093/cid/ciaa1866. (18 December 2020).
   https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1866/6041697