The first episode of SARS-CoV-2 infection was in August 2020. The patient underwent a pre-travel COVID-19 RT-PCR test on 16th August 2020, which was positive for SARS-CoV-2 (Ct values for all positive tests are presented in
Table 1). A repeat test on 19th August 2020 was negative. She was entirely asymptomatic during this episode and self-isolated, and received care at home. Treatment included Tab. Ivermectin and Cap. Doxycycline. Serological testing was performed several times after this episode and before vaccination and the patient was seronegative (details are presented in
Table 1).
On 1st February 2021, she received the first dose of COVISHIELD (Oxford-Astra Zeneca COVID-19 vaccine). On 18th February she was seropositive. On 15th March 2021, she received her second dose of COVISHIELD and was seropositive 6 days later on March 21st. On April 7th, 3 days before the onset of symptoms in the first breakthrough episode, serology was repeated and was positive but with a reduced index (details are presented in
Table 1).
The second episode of SARS-CoV-2 infection, which was the first breakthrough infection, was in April 2021. On April 10th, the patient developed acute abdominal pain, fever, myalgia, and fatigue. The pain was in the epigastric region, acute in onset, dull aching in character, and localized. The pain was associated with tenderness but not associated with nausea, vomiting, and change in bowel or bladder habits. The pain was initially mild in intensity but progressed over the next 2 days to become severe. It resolved completely in another 3 days after starting treatment as described below. On April 10th, a few hours after the onset of abdominal pain, the patient had a single fever spike of 101°F. Fever resolved with paracetamol without any further spikes. Two days after symptom onset, the patient developed severe body ache and extreme exhaustion that persisted for 10 days, at which point all symptoms resolved, and the patient felt completely well. She did not experience sore throat, cough, breathlessness, nasal congestion, rhinorrhoea, change in smell or taste at any point in the illness. Pulse oximetry was performed daily during this episode, and her oxygen saturation was normal throughout, with values between 97 and 99%.
Two days after symptom onset (April 12th), she underwent RT-PCR testing, which was positive for SARS-CoV-2 RNA. This sample was retrieved for whole genome sequencing as detailed later. RT-PCR was negative for SARS-CoV-2 RNA 4 days (April 14th) and 14 days (April 24th) after symptom onset. Ct values are presented in
Table 1.
During this episode, she had serial blood tests, including C-reactive protein (CRP). CRP peaked on April 13th, and reduced progressively to normal on April 21st. Details for CRP are presented in
Table 2.
Three days after symptoms onset (April 13th), she underwent chest high resolution computed tomography (HRCT), which revealed subtle ill-defined ground glass opacification in the posterior and lateral basal segments of the bilateral lower lobes suggestive of viral pneumonitis, with a CT severity score of 2/25.
She self-isolated and received treatment at home. Treatment included T. Azithromycin, T. Ivermectin, T. Rivaroxaban, and T. Prednisolone (40 mg daily for 10 days). By April 21st, her symptoms had resolved completely, and RT-PCR on April 24th was negative for SARS-CoV-2 RNA.
The third episode of SARS-CoV-2 infection, which was the second breakthrough infection, was in late April 2021, and continued into May with some symptoms persisting until mid-June. On April 25th, the patient developed body ache, fatigue, and headache, which was later accompanied by cough, fever, rhinorrhea, vomiting, and breathlessness. Initially, the patient experienced body ache, fatigue, and headache and thought it was related to the prior infection. However, over the next 2 days, she developed a cough, initially dry but which over the next 2 days became productive with expectoration of small volumes of yellowish sputum. The cough worsened with bouts of coughing coming more frequently and lasting longer. Over the next few days, it progressed so that the patient would start coughing continuously on walking just a few steps or with the slightest exertion. Cough was not associated with hemoptysis or chest pain. Seven days into this episode (May 2nd), the patient developed a fever, which was continuous, and was associated with chills and rigor. Fever spikes continued for 2 weeks.
One week after the onset of fever (May 10th), the patient started to feel breathless at rest, and for the first time, pulse oximetry revealed hypoxia with oxygen saturation of 93%. She was hospitalized on the same day and started on supplementary low flow oxygen therapy. She remained in hospital for 5 days, and her oxygen saturation fluctuated between 93 and 97%. After 5 days of hospital care, she was discharged; fever and breathlessness had resolved, and oxygen saturation was normal on room air. Residual fatigue, body ache, and cough persisted for a month after discharge.
A day after the onset of fever (May 3rd), the patient underwent RT-PCR for the first time in the third episode, and it was positive for SARS-CoV-2. This sample was retrieved for whole genome sequencing as detailed later. Serial RT-PCR tests were positive with a reduction in Ct values. RT-PCR was negative on discharge from the hospital on May 15th. Details of RT-PCR tests and Ct values are presented in
Table 1.
The patient underwent serial blood investigations in the third episode. CRP, which was normal on April 24th, increased progressively over the episode. CRP was elevated on April 30th and peaked on May 10th. Thereafter as the patient clinically improved, the CRP reduced progressively. Interleukin-6 progressively increased to a peak on May 10th. D-dimer was normal on the day of hospitalization (May 10th), indicating that the breathlessness and hypoxia were not due to a pulmonary embolus. D-dimer increased to a peak on May 15th. Details for CRP, IL-6, and D-dimer are presented in
Table 2.
Serial chest HRCT was performed during this episode. An HRCT chest on May 3rd reported no abnormalities with a CTSS of 0/25. HRCT chest on May 8th revealed COVID-19 pneumonia with a CTSS of 7/25. HRCT chest on May 11th revealed progression of pulmonary involvement with multiple non-segmental areas of ground glassing and associated interlobular septal thickening involving bilateral lungs with intervening areas of consolidation with an increased CTSS of 12/25.
Treatment in the hospital included low flow oxygen therapy, Remdesivir, Dexamethasone, Enoxaparin, Paracetamol, and Cefepime. In addition, the patient, required insulin to manage hyperglycemia secondary to steroids. On discharge, the patient was prescribed Rivaroxaban, Novorapid, and a tapering dose of Prednisolone.
The patient made a complete recovery, and subsequent serological testing demonstrated boosting of humoral immunity (details have been presented in
Table 1).
