Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)

* INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet all the following criteria: * Stated willingness to comply with all study procedures and availability for the duration of the study. * Male or female, aged at least 18 or older. * Provides documentation of at least one positive COVID-19 Test. Approved test can include the following: * PCR, NAA, or other EUA Approved test to confirm active COVID infection. * A positive anti-nucleocapsid antibody test. * A positive home Antigen test is acceptable when documentation of a photograph of the test with a phone-based date and time stamp is provided. * A positive anti-Spike antibody test is accepted in unvaccinated individuals or those who had antibody testing prior to vaccination. * Previously diagnosed with mild-moderate COVID-19 (WHO Clinical Progression Scale between 2-5. Participants who had severe acute COVID-19 requiring hospitalization or ICU care are excluded. * If participants had multiple SARS-CoV-2 infections, they would need to be at least 6 months after the last infection. * All participants would need to have a negative SARS-CoV-2 nasal swab at the time of enrollment. Documentation of the SARS-CoV-2 infection that led to development of PASC confirmed either by a positive testing by a commercial laboratory or a positive home test followed by confirmatory nucleocapsid antibody testing. * Exhibiting persistent neurologic symptoms evidenced by a self-reported illness narrative of the development of persistent PASC symptoms after recovering from a SARS-CoV-2 infection. These include symptoms such as fatigue, cognitive difficulties, sleep disturbances, orthostatic intolerance, and any ongoing issues with gait instability, vision, speech, swallowing, sensation, or strength. Symptoms must persist for at least 6 months after the diagnosis of acute COVID-19. * All participants will have PD-1 expression on CD8 T cells that is one SD above the mean value of normal controls as established in the SINS Lab and published previously. * Moderate to severe PASC symptom severity, as determined using PCFS (minimal score of 3). * Ability of participant to understand and sign a written informed consent document. * Prior completion of a clinical brain MRI after the diagnosis of COVID-19, or willingness to complete a brain MRI. * Agrees not to have vaccinations over the course of the study. * Participants of childbearing potential must agree to use a combination of contraception (defined as two forms of effective birth control) or have had surgical sterilization, from the time of enrollment until 4 months after the dose of study drug. * Participants capable of sperm donation must agree to not donate sperm from the time of enrollment until 4 months after the dose of study drug. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * For participants who have not completed a brain MRI since onset of symptoms: inability to complete brain MRI with gadolinium including contraindicated metal in the body, prior allergic reaction to gadolinium, eGFR \<45 mmol/L, or claustrophobia that is unable to be adequately treated with a low dose oral benzodiazepine. * Contraindication to a research lumbar puncture, including use of anticoagulant medication, platelets \< 50,000/uL, PT or PTT \>1.5 x ULN for the NIH Clinical Center, if risk of lumbar puncture is increased for other reasons such as space occupying lesion, skin infection at site of the puncture or otherwise inability to complete the procedure. * A condition that would significantly confound interpretation of the clinical and research tests as determined by the study investigators. This could include traumatic brain injury, substance use disorder, active malignancy, systemic immunologic disorders, current or previous long-term immune suppressive therapy. * Any premorbid medical condition that would potentially cause fatigue and exercise intolerance. This includes many chronic medical diseases, such as congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, severe arthritis, uncontrolled asthma, renal failure, fibromyalgia, and ME/CFS. * Symptom severity that makes it impossible for the participant to travel to NIH. * Received a SARS-CoV-2 vaccine dose within less than 4 weeks of enrollment or is planning for any additional vaccines during the study. * Prior treatment for PASC with immunomodulatory therapies such as check point inhibitors which in the opinion of the investigators could impact the outcome of this study. * Current medications include oral steroids or other immunosuppressive medications which in the opinion of the investigators could impact the outcome of this study. * Active participation in a clinical protocol which includes any intervention that may affect the results of the current study. * Abnormal anti-thyroid panel (anti-TPO and anti-TG) test at screening visit. * ANA titer of 1:80 or greater, positive anti-CCP. * Abnormal screening blood tests exceeding any of the limits defined below or as deemed exclusionary by the investigators on review at baseline: * Aspartate aminotransferase and alanine aminotransferase values \>2x upper limit of normal precluding the use of acetaminophen * Fasting triglyceride \> 300 mg/dL. * Total bilirubin \>2x upper limit of normal (unless participant has Gilbert syndrome) * Creatinine Clearance or eGFR \<60 ml/minute (adjusted for race) * Hemoglobin \< 10 g/dL * Absolute neutrophil count \< 1000/microliter * Platelet count \<130,000/mm3 (if platelet clumping is present on hematology slide review, platelet count \<100,000/mm3 is considered exclusionary to study) * Hemoglobin A1c \>= 6% * Thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) within normal limits. If TSH is not within normal limits then the participant may be eligible if thyroxine (T4) is within normal limits. Participants are not excluded if they are on a stable dose of replacement thyroid medication; dose may be adjusted as needed. * Previously documented anaphylaxis or severe systemic reaction to check point inhibitors, acetaminophen, or diphenhydramine. * A severe psychiatric condition, which based on the assessment of the study investigators, will impact the ability to complete the study. * Pregnancy or planning to get pregnant. * Currently lactating/breastfeeding. * Current or previous malignancy. A history of malignancy that has fully resolved with surgical resection only (e.g. no chemotherapy, radiation therapy, or immunotherapy) will be allowed. * Current or past substance use disorder within last five years. Marijuana use within the past five years will not be an exclusion. * Infection with HIV, tuberculosis, hepatitis B or C.