Re-infection with severe acute respiratory syndrome with new coronavirus 2 (SARS-CoV-2) is increasingly reported. However, no case report described a different manifestation in the second episode than the initial one. The patient is a 31-year-old Caucasian male with a history of SARS-CoV-2 infection, which resulted in admission to the intensive care unit for respiratory support due to coronavirus disease 19 (COVID-19). Seventy-nine days after discharge from the hospital, he developed malaise, an aphthous ulcer on the gingiva, and a desquamation lesion of the palm. It was confirmed that SARS-CoV-2 was re-infected by nasal swab PCR. His recovery from reinfection was uninterrupted without the need for inpatient care and a smooth return to his daily routine. Despite controversy about persistent immunity to neutralizing antibodies against SARS-CoV-2, reports of recurrent COVID-19 are increasingly published with variable time intervals and presentations. This case report encourages clinicians to remain vigilant about the potential risk of re-infection with SARS-CoV-2, even with different symptomatology, as vaccination efforts grow globally.
The coronavirus disease pandemic 19 (COVID-19), caused by severe acute respiratory syndrome new virus 2 (SARS-CoV-2), continues despite the launch of global vaccination.1 In addition to the exhausting length and enormous burden, the growing number of patients with SARS-CoV-2 reinfection is worrying.2-4 A systematic review of the literature estimated the incidence rate of recurrent positivity for SARS-CoV-2 at 14.8%.5
Most case reports described a more serious clinical presentation for SARS-CoV-2 re-infection than the initial encounter. However, to our knowledge, there is no report that would describe a case of re-infection with a different clinical presentation than the initial episode.
2 CASE PRESENTATION
The patient is a 31-year-old white man who serves as a doctor staying at a university hospital. He was diagnosed with laboratory-confirmed COVID-19 on July 25, 2020. The patient initially had a three-day history of fever (oral temperature 99.8 ° F), malaise, cough, shortness of breath, anosmia, and dropped O.2 saturation up to 88% in room air. Computed tomography (CT) of the chest showed bilateral opacity of the lungs from ground glass (Figure 1). He was admitted to the intensive care unit (ICU) and received supportive treatment with additional oxygen 3-4 l / minute, a tablet of hydroxy chloroquine 200 mg twice a day and a bottle of dexamethasone, 6 mg intravenously daily. He recovered smoothly in 1 week with 94% O2 saturation and resumed his daily routine gradually over several weeks. Subsequent polymerase chain reaction (PCR) testing on a nasal swab was negative for SARS-CoV-2, 2 weeks after discharge from the hospital.
On October 12, 2020 (79 days after the initial meeting), the patient developed fatigue followed by painful submandibular lymphadenopathy and aphthae on the gingiva (Figure 2). Two days later, he developed fever (oral temperature: 99.8 ° F) and myalgia. PCR test of nasopharyngeal swab was positive for COVID-19, and the patient was quarantined to take a 250 mg tablet of naproxen every 12 hours for 4 days. Since he did not have difficulty breathing, he did not seek any medical help, so his chest was not filmed. Although his symptoms improved over the next 3 days, he developed desquamation of his palms and fingers (Figure 3). The changes in the skin quickly improved over the course of the week, as did his other symptoms. The patient did not need any other medications. A follow-up visit after 1 month and 6 months revealed complete resolution of symptoms and return to daily routine.
As our knowledge of risk factors for recurrence of COVID-19 and other related parameters develops, data suggest temporary immunity to SARS-CoV-2 antibodies in unvaccinated individuals.6 and the emergence of escape viral mutants as potential mechanisms for recurrent cases.7 Our case developed re-infection with SARS-CoV-2 after an initial episode of severe disease and a two-month disease-free interval. The second episode was significantly milder and did not require inpatient medical care, but was relatively different in presentation from the initial episode. In a follow-up study at Oxford University hospitals in the United Kingdom, Lumley and colleagues measured spike antibodies and anti-nucleocapsid IgG in 12,541 healthcare workers and followed them for 31 weeks.6 The authors found that out of 1265 seropositive cases, 88 developed seroconversion during the follow-up period. On the other hand, 223 seronegative subjects developed a positive PCR test (1.09 per 10,000 days of risk), of which 44.84% were asymptomatic and 51.6% symptomatic. This differed significantly from the only 2 seropositive cases, which became PCR positive during the follow-up period (0.13 per 10,000 days at risk). Although antibodies against SARS-CoV-2 on average provided immunity against re-infection for 6 months, our case report together with others raises questions about the generalization of such short-term protection.4, 5 However, none of these cases followed the evolution of neutralizing antibodies or their titers against SARS-CoV-2 from initial infection to the time of re-infection.
Genomic analysis of SARS-CoV-2 at two different times by a 25-year-old from Washoe, Nevada, revealed genetically significant differences between the two species.4 Unlike our patients, the second episode was more difficult in terms of clinical symptoms. Further case reports also show a decrease in antibody titer to coincide with re-infection with SARS-CoV-2.2, 3, 8 A report from the Hong Kong case showed that the initial mild infection with SARS-CoV-2 did not produce an effective neutralizing antibody, which five months later, although completely asymptomatic, resulted in re-infection with the virus.2 Another case from the Netherlands showed a more serious presentation of COVID-19 recurrence compared to the episode with the index.3 Although the latter patient was weakened by immunity due to recent chemotherapy for Waldenström’s B-cell-depleting macroglobulinemia, an effective innate immunity or T-cell response may have acted as a lifesaver. The same path can be imagined for the depiction of a case from Hong Kong in which no effective neutralizing antibody was detected in any episode. Unfortunately, our current laboratory setting did not allow the measurement of anti-SARS-CoV-2 antibody titers from index infection to COVID-19 recurrence, nor did it allow genomic analysis of the causative agent in these two different episodes.
The time interval between the initial SARS-CoV-2 infection and the second episode has been reported differently in the literature.3-5, 8 Although the duration of immunity to spike antibodies or antinucleocapsid IgGs was shown to be at least 6 months, a systematic review of reported cases of SARS-CoV-2 re-infection estimated this interval at 35.4 days.5 The review also found that younger age and longer time to become PCR negative were significantly associated with a higher risk of SARS-CoV-2 re-infection, while severe disease may play a protective role.
The report of our case supports the growing suspicion of persistent immunity against SARS-CoV-2. Although our patient presented differently in the second episode than the initial one, the clinical manifestation was clinically less serious. The time from initial infection to recurrent episode was above average time, as noted in the literature. However, we could not examine the evolution of neutralizing antibodies in this time interval because the titer in our case was not measured. Although current efforts in global vaccination against SARS-CoV-2 are ongoing, clinicians should be wary of variations in individuals ’responses to infection and the potential risk of re-infection despite receiving the vaccine. This is especially important when reading news about new variants of SARS-CoV-2, which look more contagious.9
CONFLICT OF INTERESTS
The authors do not have a conflict of interest in any form.
CONTRIBUTION OF THE AUTHOR
SS: reviewed the literature, developed the structure of the study, drafted the manuscript, and approved its final version for intellectual content. SK: developed the idea of the study, reviewed the literature, participated in the drafting of the manuscript and approved its final version for intellectual content. ET: participated in the development of the study concept, patient data collection and manuscript development, and approved its final version for intellectual content. SK: participated in the development of the study concept, patient data collection and manuscript development and approved its final version for intellectual content. MN: participated in the development of the study concept and revision of the manuscript and approved its final version for intellectual content. NS: participated in the collection of patient data and revision of the manuscript and approved its final version for intellectual content.
We obtained the patient’s consent to publish his clinical case report in an unidentified manner and without disclosing his personal information.
This study does not have any data repositories or sources that could be accessed.
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- 9 New Covid – 19 Variants of Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019‐ncov/transmission/variant.html. Published 2021. Accessed March 1, 2020.