SIRVA; A PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND EFFICACY OF SARS-COV-2 RNA VACCINE CANDIDATES AGAINST COVID-19 IN HEALTHY INDIVIDUALS  This is a report from an interventional study source sponsored by BioNTech, managed and reported by Pfizer on the sponsors behalf. A 30-year-old female subject received the first dose of blinded vaccine (BNT162; PLACEBO) on 17Aug2020 at 17:01 and second dose on 09Sep2020 at 15:20, both intramuscularly on the left deltoid as single doses for COVID-19 immunization. Medical history included ongoing allergies. Ongoing concomitant medication included cetirizine hydrochloride (ZYRTEC) for allergies. The subject had no other vaccine administered neither on the same day nor within four weeks prior to the administration of the investigational vaccine and no relevant family medical history. The subject had no history of trauma, heavy lifting or vigorous exercise, and the subject was believed to be right-handed. On 09Sep2020 at 18:00, the subject experienced shoulder injury related to vaccine administration (SIRVA) after the second vaccine dose, which was considered as a medically significant event and required physician office visit. The clinical course was as follows: on 09Sep2020 at evening, the subject had pain in the whole left arm. She noted that the band-aid was very high on her arm. She had some soreness of her upper arm and very limited range of motion for the first few days, with burning pain down her arm. Initially she had some tingling down her arm, but this had resolved. On 15Sep2020, the subject had a sensation of numbness which affected her arm and hand, with a sensation of loss of dexterity which was notable when typing. The subject informed that she was improving gradually, especially in terms of pain, but still had a significant limitation in range of motion and daily activities. On exam she did not have any obvious swelling, color change, bruising, or tenderness over the left deltoid. She could raise her left arm slightly higher than 90 degrees and with assistance could lift higher, but this caused significant discomfort. She could not extent her left arm behind her back well. Strength was 5/5. When moving her arm against resistance, she experienced pain down her arm and increased sensation of numbness. The investigator discussed a possible diagnosis of SIRVA. The subject was aware that it could be self-limiting and might last for some time. The subject expressed an interest to start with physical therapy and informed the investigator that she would try to arrange for such. The subject was seen by a neurologist who noted the following findings: motor function: normal muscle bulk and tone. No apparent fasciculations. No scapular winging. Shoulder abduction limited to 70 degrees; shoulder internal rotation limited as well but able to put her left hand behind her back. Manual muscle testing revealed the following MRC grades (R/L when applicable): Internal rotation 5/4+, External rotation 5/4 SA 5/4+, EF 5/5-, EE 5/4+, (proximal muscles limited by pain), pronation 5/4, WF 5/4+, WE 5/5, FF 5/5, FE 5/4+, FPL 5/4+, APB 5/4, IO 5/4+, HF 5/5, KE 5/5, KF 5/5, ADF 5/5, APF 5/5, toe extension 5/5, toe flexion 5/5. The neurologist considered two diagnoses: SIRVA and immune-mediated brachial plexus neuropathy (IBPN) (also known as Parsonage-Turner Syndrome) and noted that the clinical picture could demonstrate components of both. An electromyography (EMG) was recommended to determine if nerve involvement and if so, to what degree. Physical therapy was also recommended which the neurologist noted that the subject had already started. On 02Oct2020, the EMG was performed and stated as follow: "Since onset, both the pain and limitation in range of motion have improved. The greatest improvement was in the shoulder and upper arm, and less so in the hand or fingers. EMG results: SENSORY NCS: Nerve/sites: left (L) median wrist: Rec. site: digit 2, Dist (cm): 14, Lat (ms): 2.3, Peak (ms): 3.1, Amp. (uV): 51.6, Dur. (ms): 1.6, Vel (m/s): 59.7, and temperature (temp.) (centigrade): 30.4; L ulnar wrist: Rec. site: digit 5, Dist: 11.5, Lat: 2.0, Peak: 2.5, Amp.: 54.9, Dur.: 1.1, Vel: 58.1, and temp.: 30.8; L radial thumb forearm: Rec. site: thumb, Dist: 10, Lat: 1.8, Peak: 2.2, Amp.: 17.0, Dur.: 1.6, Vel: 56.5, and temp.: 31; L lateral antebrachial cutaneous lat elbow: Rec. site: forearm, Dist: 10, Lat: 1.6, Peak: 2.1, Amp.: 40.0, Dur.: 1.1, Vel: 64.0, and temp.: 31.2; L medial antebrachial cutaneous med elbow: Rec. site: forearm, Dist: 8, Lat: 1.3, Peak: 1.9, Amp.: 19.4, Dur.: 1.2, Vel: 61.4, and temp.: 31.3; right (R) medial antebrachial cutaneous med elbow: Rec. site: forearm, Dist: 8, Lat: 1.5, Peak: 2.0, Amp.: 15.3, Dur.: 1.1, Vel: 54.9, and temp.: 31.3. R lateral antebrachial cutaneous lat elbow: Rec. site: forearm, Dist: 10, Lat: 1.5, Peak: 2.0, Amp.: 38.9, Dur.: 1.0, Vel: 66.2, and temp.: 31.3; R radial - thumb forearm: Rec. site: thumb, Dist: 10, Lat: 1.6, Peak: 2.2, Amp.: 17.8, Dur.: 1.5, Vel: 64.0, and temp.: 31.3; R ulnar wrist: Rec. site: digit 5, Dist: 11.5, Lat: 2.0, Peak: 2.7, Amp.: 55.0, Dur.: 1.4, Vel: 56.6, and temp.: 31.2. MIXED NCS: Nerve/sites: L median, medial palm: Rec. site: wrist, Dist: 8, onset Lat: 1.3, Pk lat (ms): 1.7, Amp.: 100.9, Dur.: 0.99, Vel: 64.0, and temp.: 30.2. MOTOR NCS: Nerve/sites: L medial - APB wrist: Rec. site: APB, Dist: 6, Lat: 2.6, Peak: 10.0, Amp. (mV): 36.2, Area (mVms) Dur.: 6.0, Vel: not provided, and temp.: 31.3; L medial - APB elbow: Rec. site: APB, Dist: 23, Lat: 6.5, Peak: 9.9, Amp. (mV): 34.8, Area (mVms) Dur.: 6.2, Vel: 58.9, and temp.: 31.3; L ulnar -ADM wrist: Rec. site: ADM, Dist: 6, Lat: 2.0, Peak: 9.9, Amp. (mV): 24.9, Area (mVms) Dur.: 4.9, Vel: not provided, and temp.: 31.5; B. ulnar Gr: Rec. site: ADM, Dist: 18, Lat: 5.2, Peak: 9.0, Amp. (mV): 24.9, Area (mVms) Dur.: 5.2, Vel: 55.7, and temp.: 31.6; A. ulnar Gr: Rec. site: ADM, Dist: 10, Lat: 6.7, Peak: 8.7, Amp. (mV): 22.2, Area (mVms) Dur.: 5.4, Vel: 68.6, and temp.: 31.3. EMG summary table no spontaneous (Fibs/PSW, Fasc) no MUAP (Amp, Dur., PPP) and no Recruitement (pattern, effort) for muscle, L. biceps brachii, L triceps brachii, L pronator teres, L flexor carpi radialis, L first dorsal interosseous and L abductor pollicis brevis. Summary: A. needle EMG examination of the left upper extremity was normal for all muscles sampled. The deltoid was avoided due to suspected prior injury to the area. B. Normal median sensory potential on the left. C. Normal and symmetric ulnar sensory potentials bilaterally. D. Normal and symmetric radial sensory potentials. E. Normal and symmetric medial and lateral antebrachial cutaneous sensory potentials bilaterally. F. Normal medial mixed palmar latencies on the left. G. Normal median and ulnar motor conduction studies on the left. Conclusion: This was a normal study. 1. There was no neurophysiologic evidence of a brachial plexopathy on the left. 2. There was no neurophysiologic evidence of median nerve dysfunction at the wrist on the left. 3. There was no neurophysiologic evidence of ulnar nerve dysfunction across the elbow on the left. 4. There was no neurophysiologic evidence of a cervical radiculopathy on the left. Clinical correlation was recommended". On 07Oct2020, the neurologist considered that SIRVA was the most likely diagnosis based on the clinical improvement and that the EMG result did not reveal nerve involvement in the neurons tested. The subject reported continued improvement especially of the upper arm with increased range of motion but continued decreased dexterity of the left hand. The subject was attending physical therapy twice weekly and reported satisfaction with the gradual and continued improvement the subject was experiencing. On 03Nov2020, the subject informed that she had completed 5 weeks of physical therapy, that her improvement was significant but that she was not back to her usual state of health. The action taken with the blinded vaccine (BNT162; PLACEBO) in response to the event was not applicable.  Subject was felt much better and had returned to baseline after completing physical therapy. The outcome of the event was completely recovered on 08Feb2021.  The investigator considered there was a reasonable possibility that the event SIRVA was related to the second dose blinded vaccine (BNT162; PLACEBO) and to a clinical trial procedure (vaccine administration) but considered it unrelated to concomitant medications.  On 21Sep2020, the blinded code was broken due to serious, related, unexpected event.  Follow-up (30Sep2020, 05Oct2020 and 07Oct2020): New information reported includes: reporter's details, medical history, laboratory data, treatment details and updated reaction data.   Follow-up (10Nov2020): New information reported includes: clinical course (subject's current status).  Follow-up (10Dec2020):  This is a follow-up report based on the receipt of the publication. No further information provided.  Follow-up (09Mar2021): New information reported includes: adverse reaction (event onset date specified, outcome of event updated to recovered) and clinical course. ; Sender's Comments: The event SIRVA is unlisted in the Single Reference Safety Document (SRSD) of the Investigational Product blinded therapy vaccine (BNT162; PLACEBO) based on the information currently available.  There is a reasonable possibility for the event SIRVA to be related with the blinded therapy vaccine (BNT162; PLACEBO). Based on the reported location of the band-aid, i.e., high up on the subject's arm, and the occurrence of the SIRVA, it appears that the vaccine was erroneously administered into or near the shoulder joint capsule. Postulated in the medical literature, unintentional injection of vaccines into the shoulder joint synovial tissues may result in an immune-mediated inflammatory reaction causing SIRVA. Reports of SIRVA has been associated with poor techniques in administering vaccines in general. The event is not considered a unique response to this specific vaccine (BNT162; PLACEBO).  The impacts of this report on the benefit/risk profile of the Pfizer product and on the conduct of the study is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committee and Investigators, as appropriate.