Case 4
The final case describes a 50-year-old white male patient with a history of hypertension and hyperlipidemia who presented in March 2020 after developing respiratory symptoms, fevers, chest pain, and myalgias a week following a COVID-19 exposure at his place of work. He returned 2 days later, had a normal chest x-ray, but tested positive for SARS-CoV-2 by RT-PCR. He was admitted to the ICU for persistent fevers and progressive shortness of breath, although he was never hypoxic. He was treated empirically with azithromycin for suspected superimposed community-acquired pneumonia and discharged home two days later. He was enrolled in an observational study and had a nasopharyngeal sample taken 2 weeks after his initial positive test that was still positive for SARS-CoV-2 by qRT-PCR (VL 7,128 copies/mL). He had lingering symptoms of cough, fatigue, and sore throat from April to June, but 5 serial nasopharyngeal samples throughout April and May tested negative by qRT-PCR. During a clinical follow up visit in June, he had a routine nasopharyngeal swab that tested positive for SARS-CoV-2, and he developed a dry cough and loss of taste two days later. He recovered without need for hospitalization or treatment and tested negative for SARS-CoV-2 a week later. The interval of about 3 months in between his two positive tests as well as 5 negative quantitative PCR test results in this interim period suggest true reinfection. In terms of serologic responses, he had detectable levels of IgG from March to October, which peaked at 3,040.6 AU/mL in April and remained over 385 AU/mL through October. While IgM levels were no longer detectable in this patient after May, he had IgG anti-spike protein levels of 1,030.2 AU/mL in late June during his second COVID-19 infection (Figure 1 ). Overall, while this patient suffered from hypertension, he lacked other significant comorbidities that might explain why he was more susceptible to reinfection.
In summary, we report 4 cases of SARS-CoV-2 reinfection in patients across the spectrum of age and health. For cases 1 and 2, a clear lack of serologic response to initial infection may have contributed to their risk, although why the healthy patient in case 1 failed to mount an effective antibody response is unclear. However, for Case 4, a strong serological response was measured after his first infection event which persisted during and after his reinfection, suggesting that anti-spike RBD antibodies alone are not sufficient for protection. Unfortunately, samples were not available to demonstrate differences in viral strains across episodes for these patients, but there is no known data indicating widespread circulation of substantially different SARS-CoV-2 variants in North Carolina during these timeframes. This suggests that immunologic variables rather than virologic causes are primarily responsible for these reinfection cases. While reinfection does not yet appear to be a common phenomenon in the current pandemic, an improved understanding of the character and duration of protective immunity and risk factors for poor serologic responses to infection and vaccination has major consequences for our handling of the pandemic moving forward.
Fig. 1 Serologic Responses Over Time. Shown are IgG antibody levels against the SARS-CoV-2 spike receptor binding domain (RBD) at each time point in Case 1, the husband of Case 1, and Case 4 relative to each individual’s first infection symptom onset (day 0). Case 1 and her husband had serial serological testing from April to October 2020 and Case 4 had serial serological testing from March to October 2020