Veena Episode 2 Pdf Free 25 UPDATED
This seven-episode Western mini-series is a great example of how TV is attracting some of the very best feature writers. In this case, Scott Frank wrote the series exclusively for Netflix and it went on to win many awards including Outstanding Writing for a Long Form from the WGA West.
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Findings: The patient had three RT-PCR confirmed SARS-CoV-2 infections. Two breakthrough infections occurred in quick succession with the first over 3 weeks after complete vaccination with COVISHIELD and despite post-vaccination seroconversion. The first breakthrough infection was due to the Alpha variant and the second due to the Delta variant. The Delta variant infection resulted in hypoxia, hospitalization, and illness lasting seven weeks. Serial serology, acute phase reactants, and chest imaging supported WGS in establishing distinct episodes of infection. WGS established a fully vaccinated family member as the index case.
Breakthrough infections are tempered by vaccines and are generally mild (5). Vaccines also reduce the risk of onward transmission (6), but it is unclear whether this holds true for the Delta variant and all vaccines. Reinfections are thought to be relatively rare, but difficulty in retrieving paired samples from different episodes for whole genome sequencing (WGS) makes it challenging to establish reinfection. In the context of VOCs, reinfections are possible and likely more common than we think. Even when reinfections are WGS proven, serial serology, inflammatory markers, and radiological imaging are usually unavailable. This limits our understanding of these rare but immunologically significant episodes.
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 101F. 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%.
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.
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.
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.
The first breakthrough infection was symptomatic and was caused by the Alpha variant. Acute-phase reactant CRP was elevated, and HRCT chest showed COVID-19 pneumonia with CTSS 2/25. As the patient had radiological evidence of lower respiratory tract disease, this was a moderate illness. The patient recovered with treatment which included a course of oral steroids. In this symptomatic episode, the high Ct values were congruent with post-vaccination breakthrough infections that tend to have a lower viral load (23).
The time interval between the two breakthrough infections was short, with just 4 days between symptom resolution in the first and symptom onset in the second. However, several different lines of evidence show that the second and third episodes were distinct infections caused by different variants. Samples from the two episodes show two different variants that fit the criteria for best evidence for reinfection (24). However, the time period between the positive tests in the two episodes was just 21 days. In addition to genomic evidence, there was evidence from clinical history, negative RT-PCR tests, acute phase reactants, and chest imaging that support resolution of the first infection before a new infection occurred. Clinically the patient's symptoms had completely resolved for 4 days before symptoms reappeared in the third episode. There were two negative RT-PCR results between the second and third episode. CRP had normalized between the episodes. Chest imaging (HRCT) showed resolution of pulmonary involvement between the two episodes with new and progressive changes during Delta variant infection.
The short time interval between the two episodes of breakthrough infection highlights that the existing criteria for reinfection that use predefined periods may result in missing reinfections by the Delta variant. Following time-based criteria, such as those in the US CDC investigation protocol for reinfections (24), would have resulted in missing this important case of breakthrough reinfection. With the emergence of VOCs, clinicians need to be alert to the possibility of reinfections occurring in close succession. It would be prudent to use clinical, molecular, biochemical, serological, and radiological clues to assign reinfections.
The first breakthrough infections occurred over three and a half weeks after the second dose of COVISHIELD and documented seroconversion with anti-RBD IgG antibodies. Serology on March 21st, 6 days after the second dose, showed a CLIA index of 5.84. Repeated serology on April 7th, 3 days before symptoms onset in the first breakthrough episode, showed a decreased CLIA index of 2.85. It is possible that the decrease in antibodies may have contributed to increased susceptibility to Alpha variant infection. After the first breakthrough infection by the Alpha variant, there was the boosting effect seen on serology. Breakthrough reinfection with Delta variant occurred despite this. There may be higher humoral correlates of protection for some VOCs.
AMC announced the series's cancellation in July 2012, but picked it up for a third season after a renegotiation with Fox Television Studios and Ne