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