Real World Evidence of Effectiveness of COVID-19 Vaccines and Anti SARS-CoV-2 Monoclonal Antibodies Against Post-Acute Sequelae of SARS-CoV-2 Infection

BackgroundWe evaluated the effectiveness of COVID-19 vaccines and monoclonal antibodies (mAb) against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), an emerging public health problem. Methods and FindingsIn a retrospective cohort study, we identified patients with clinically significant PASC using a COVID-19 specific, electronic medical record-based surveillance and outcomes registry from an 8-hospital tertiary healthcare system in the greater Houston metropolitan (primary analyses). Analyses were then replicated across a global research network database. We included all adults (>= 18) who survived beyond 28-days of their index infection. PASC was defined as experiencing constitutional (palpitations, malaise / fatigue, headache) or systemic (sleep disorder, shortness of breath, mood / anxiety disorders, cough, and cognitive impairment) symptoms beyond 28-day post-infection period. Instances of PASC were excluded if the symptoms were present pre-COVID or if they resolved within four weeks of initial infection. We fit multivariable logistic regression models and report estimated likelihood of PASC associated with vaccination or mAb treatment as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Primary analyses included 53,239 subjects (54.9% female), of whom 5,929, 11.1% (CI: 10.9 - 11.4), experienced PASC. Both, vaccinated breakthrough cases (vs. unvaccinated) and mAb treated patients (vs. untreated) had lower likelihoods for developing PASC, aOR (CI): 0.58 (0.52, 0.66), and 0.77 (0.69, 0.86), respectively. Vaccination was associated with decreased odds of developing all constitutional and systemic symptoms except for taste and smell changes. For all symptoms, vaccination was associated with lower likelihood of experiencing PASC compared to mAb treatment. Replication analysis found almost identical frequency of PASC (11.2%) and similar protective effects against PASC for the COVID-19 vaccine: aOR (CI) 0.25 (0.21 - 0.30) and mAb treatment: 0.62 (0.59 - 0.66). DiscussionAlthough both COVID-19 vaccines and mAbs decreased the likelihood of PASC, at present, vaccination is the most effective tool to potentially prevent long-term clinical and socio-economic consequences of COVID-19.