Reinfection of COVID‐19 after 3 months with a distinct and more aggressive clinical presentation: Case report

Abstract

The coronavirus disease 2019 (COVID-19) pandemic began in December 2019 in Wuhan, China. Since then, it has rapidly spread across the globe and impacted several countries. Brazil has more than 5.5 million COVID-19 confirmed cases, almost 160,000 deaths and is the leader in numbers of health care professionals infected. Most recent studies suggest that immunity can be developed after an episode of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection. This brings a false sense of safety for professionals who have already been infected and have recovered from the disease. They return to the battlefields exposed to high viral load, often without adequate protection. A 36-year-old female medical doctor, without comorbidities, presented on 20th March 2020 with rhinorrhea and sore throat followed by low fever, diarrhea, asthenia, and mild headache until the seventh day of symptoms when reverse transcription polymerase chain reaction (RT-PCR) was obtained by nasal swab. The RT-PCR collected on 27th March 2020 was positive for SARS-CoV2 with a log of 513 copies (detection limit of RT-PCR less than 100 copies). After 11 days of initial clinical symptoms, she presented with erythematous vesicles on her right calf, along with severe musculoskeletal pain of the lower limbs with hyperesthesia. The first serological test was performed using enzyme-linked immunosorbent assay (ELISA), 23 days after the onset of symptoms, with 0.477 immunoglobulin G (IgG) titers (negative: less than 1.00 S/CO). There was complete resolution of the symptoms 24 days after onset (Figure 1). The patient returned to medical work at COVID-intensive care unit in two hospitals. After returning to work she was tested twice for COVID by chemiluminescence method serologies. The results were both negative for IgM and IgG detection, 33 days and 67 days after the acute presentation of symptoms. Approximately 12 weeks after the first episode of COVID-19, she presented a new clinical symptomes with nasal obstruction and hyaline rhinorrhea, sudden and complete anosmia and ageusia, frontal headache, and asthenia. On the tenth day of this new clinical episode, there was worsening of prostration with persistent anosmia and ageusia. She sought emergency care on the 11th day of symptoms, where she underwent a computed tomography (CT) scan that revealed a pattern of acute viral pneumonia typical of COVID-19 (Figure 2A). The ELISA serology on the 13th day of symptoms revealed positive immunoglobulin A for COVID-19 with 4240 titers (negative: less than 1.00 S/CO). Nasal swab RT-PCR on the 11th and 13th days of symptoms were negative. d-Dimer increased to 761 ng/ml and DHL to 290 U/L, however, serum values normalized after 48 h. The neutralizing IgG titration performed by the ELISA method on the 20th day of symptoms was positive in 1173, and after 45 days was 7473 (immunity: titer greater than 1.00 S/CO). The pulmonary pathological changes identified on the chest CT practically disappeared on the twenty-fourth day after the onset of symptoms (Figure 2B). About 11 months after the first cases of COVID-19, there is still no consensus in literature of reinfection by SARS-CoV-2, although some reports around the world show strong evidence that it is happening. The strongest evidence of reinfection requires documentation of a new infection by a molecularly distinct form of the same virus after the elimination of the previous infection.1-3 Human reinfection by SARS-CoV-2 was confirmed for the first time in August 2020 in Hong Kong, through genetic sequencing of two samples collected by nasal swab from the same patient with a time difference of 142 days. There was evidence that the viral genomes belong to different lineages, one of which was more incident between March and April 2020, while the other is close to strains found today.4 As genetic difference between strains increases over time, cross-immunity between those lineages may become more difficult and different clinical pictures may occur.4 However, it is unknown how intense the second clinical episode will be. We raise the discussion whether the presence of a new mutation, such as D614G, which replicates faster in the upper airway, could be more related to pneumonia and anosmia, to the detriment of other symptoms, such as gastrointestinal manifestations.5 Despite evidence of an effective acquired immune response after COVID-19, some studies have shown that patients with mild symptoms have developed a weaker and less lasting immune response to the virus, with a decrease in the level of antibodies after 2–3 months of infection.6, 7 As the patient maintained intense exposure to COVID-19 in those 3 months between clinical episodes, had different symptoms and antibody detection only recently, this suggests reinfection by different lineages of SARS-CoV-2. Therefore, the hypothesis of herd immunity and duration of protection afforded by vaccines, is questioned. The authors declare that there are no conflict of interests. Danielle de Araujo Torres: Conceived the presented idea and elaborated the manuscript. Luciana do Carmo Bueno Ribeiro: Provided the clinical data and exams, and elaborated the manuscript. Anna Patrícia de Freitas Linhares Riello, Dafne Dain Gandelman Horovitz, Luis Felipe Ribeiro Pinto, and Julio Croda: revised the manuscript, provided critical feedback and proposed format adjustments.

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