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Symptomatic SARS-CoV-2 re-infection of a health care worker in a Belgian nosocomial outbreak despite primary neutralizing antibody response

Our take —

This study was published as a preprint and thus was not yet peer reviewed. In September 2020, a case of SARS-CoV-2 re-infection was observed in a healthy, Belgian healthcare worker in her 30s, despite a documented neutralizing antibody immune response following the first infection in March 2020. While both the primary and secondary infections were symptomatic and relatively mild, the second infection was characterized by a faster immune response and milder, less prolonged infection. Differences in the genetic sequences of the two infections, often unavailable amongst COVID-19 cases, support that these were two distinct infections. Further, at the time of the second infection, neutralizing antibodies were not detected in the nasopharyngeal swab of the health care worker, and it is likely that she was the transmission link between three other genetically linked cases within the hospital ward who had no contact with one another. These findings should be interpreted as an initial piece of evidence to help us understand how long protective immunity may last, as well as provide insights into the potential for transmission among reinfection cases to others, despite initial development of neutralizing antibodies. To date there have been 26 cases of re-infection clearly documented through genetic testing of both infections, each case providing new insights into the COVID-19 pandemic.

Study design

Case Series

Study population and setting

This study describes a case of re-infection in a healthcare worker in Belgium in September 2020, along with the associated cases in a hospital-based outbreak in an internal medicine ward. Whole genome sequencing was conducted to distinguish between persistent infection and re-infection in the re-infected case, as well as to establish chains of transmission in the outbreak.

Summary of Main Findings

The re-infected healthcare worker (HCW) was female, young (30s), healthy, and immunocompetent. During her initial infection in March 2020, she had a mild but prolonged infection in which she presented with cough, fever, headache, malaise and labored breathing and was away from work for a month. Testing three months after infection demonstrated that she had developed neutralizing antibodies. The re-infection in September 2020 was also symptomatic. While the HCW was symptomatic in both instances, the second episode was more mild and there was a rapid immune response (fast rise in serum IgG and neutralizing antibodies). Of the four other people (3 patients and 1 healthcare worker) involved in the hospital outbreak in September 2020, the three patients shared a viral genome sequence similar to that of the re-infected healthcare worker, while the other healthcare worker appears to have been infected by an external transmission source. The sequences collected from the re-infected healthcare worker and the three patients closely resembled Belgian sequences obtained in the summer months, while the sequence from the re-infected healthcare worker from her March infection resembled sequences circulating at that time. In September, the re-infected healthcare worker’s initial nasopharyngeal swabs contained virus but no neutralizing antibodies and she was the primary point of contact that was infected across the patients, suggesting likely onward transmission, though no transmission to close contacts outside of the hospital was documented.

Study Strengths

The use of whole genome sequencing, rather than a threshold number of days, allows for the cleaner distinction between re-infection and persistent infection (viral genomes are derived from different SARS-CoV-2 clades in the first and second episode). Also, because antibodies were measured 3-months post-initial infection, the authors were able to determine that the woman had at least initially developed neutralizing antibodies.

Limitations

Samples were not available from the HCW re-infected right before the second infection; thus it is not known whether the neutralizing antibodies previously measured had waned by this time (6 months post initial infection) or if they were present but just insufficient to prevent re-infection. Further, this is a single case and may not be representative of all patients with a primary COVID-19 diagnosis.

Value added

Description of this case can help us begin to understand how long protective immunity (even with an effective immune response) may last following a primary infection. These data also provide insights regarding the potential for transmission from re-infected cases to others.

This review was posted on: 7 December 2020