key: cord-0078828-u66awao9
authors: Zisis, Sokratis N.; Durieux, Jared C.; Mouchati, Christian; Perez, Jamie A.; McComsey, Grace A.
title: The protective effect of covid-19 vaccination on post-acute sequelae of covid-19 (pasc): a multicenter study from a large national health research network
date: 2022-05-07
journal: Open Forum Infect Dis
DOI: 10.1093/ofid/ofac228
sha: eed1947d2710eb9a1dd37898c5fac2542516a533
doc_id: 78828
cord_uid: u66awao9

BACKGROUND: COVID-19 vaccines have been proven to decrease the severity of acute phase infection, however little is known about its effect on Post-Acute Sequelae of COVID-19 (PASC). METHODS: Patients with confirmed COVID-19 diagnosis, minimum age of 18 years with 3 month follow-up post-diagnosis between September 21, 2020 and December 14, 2021 were identified from TriNetX research network platform. The primary outcomes consisted of new onset or persistent symptoms, new onset diagnoses, and death and were compared between vaccine and no-vaccine groups. RESULTS: At baseline, 1,578,719 patients with confirmed COVID-19 were identified and 1.6% (n = 25,225) completed vaccination. After matching, there were no differences (p > .05) in demographics or pre-existing comorbidities. At 28 days following COVID diagnosis, the incidence of hypertension was 13.52 per 1000, diabetes was 5.98 per 1000, thyroid disease was 3.80 per 1000, heart disease was 15.41 per 1000, and mental disorders was 14.77 per 1000 in the vaccine cohort. At 90 days following COVID diagnosis, the relative risk of hypertension was 0.33 (95% CI: 0.26, 0.42), diabetes was 0.28 (95% CI: 0.20, 0.38), heart disease was 0.35 (95% CI: 0.29, 0.44), and death was 0.21 (95% CI: 0.16, 0.27). Differences in both 28 and 90-day risk between the vaccine and no-vaccine cohorts were observed for each outcome and there was enough evidence (p < .05) to suggest that these differences were attributed to the vaccine. CONCLUSION: Our data suggest that COVID-19 vaccine is protective against post-acute sequelae of SARS-CoV-2 (PASC) symptoms, new onset of health conditions, and mortality.

Our data suggest that COVID-19 vaccine is protective against post-acute sequelae of SARS- CoV-2 (PASC) symptoms, new onset of health conditions, and mortality. PASC is manifesting in a wide range of persistent or new symptoms that do not resolve for 8 many months (3) (4) (5) . Indeed, up to 70% of recovered patients report fatigue, persistent loss 9 of taste or smell, shortness of breath, cough, headache, pain, and a wide array of serious 10 complications affecting the cardiovascular, pulmonary, renal, endocrinological, and 11 neurological system(2,6-11).

To face the pandemic, major international entities set vaccination as their top priority(12). 13 Worldwide, more than 9 billion vaccines doses have been administered as of 12 January 14 2022(1). Immunization is effective in preventing infection (13) We collected patients' demographics, comorbidities, COVID vaccination, as well as 9 symptoms and diagnoses prior to, at the time, and after 3 months of COVID infection. We Statistical Analysis 20 Characteristics of patients were described using mean ± standard deviation for continuous 21 variables and frequency and percentage for categorical variables (table 1). Differences

between vaccine and no-vaccine groups were calculated using independent t-test or chi-1 square. 1:1 propensity score matching using greedy nearest-neighbor method was used to 2 balance the two cohorts on age, gender, race, and comorbidities. Incidence, relative risk 3 (RR), and attributable risk (risk difference) estimates along with 95% confidence intervals 4 (CIs) were used as measures of risk at 28 days (table 2) and 90 days (table 3) following 5 COVID diagnosis. Rates were presented per 1,000 and p-values less than alpha <.05 were 6 considered statistically significant.

At baseline, 1,578,719 patients with confirmed COVID-19 were identified and 1.6% 9 (n=25225) had documented COVID vaccination. Among the vaccine cohort, the average age 10 54.82 ± 17.77 years, 59.84% (n=15094) were female, and 68.45% (n=17266) were white.

The average body mass index (BMI) was 30.20 ± 7.33 kg/m 2 , 47.36% (n=11947) no-vaccine cohorts were observed for each outcome and there was enough evidence 16 (p<.05) to suggest that these differences were attributed to the vaccine.

In our study using real-time EMR data from a large national health network, we 19 demonstrated that the vaccine was protective (i.e., RR<1.0) against mortality and each 20 incident PASC outcome and that having the vaccine is associated with a significantly lower 21 likelihood of experiencing new or persistent PASC symptoms. This suggests that patients

with COVID-19 who are not vaccinated are at greater risk of death and incident morbidity 1 during the 90 days post-infection. In this study with data from a large-scale electronic 2 health records network, we showed that individuals with COVID breakthrough infections 3 after vaccination have lower rates of PASC or long-COVID symptoms/outcomes compared 4 with propensity-matched unvaccinated COVID-infected people. As such, our work extends 5 the current data on the efficacy of COVID vaccination in acute COVID infection, to show that 6 vaccination is associated with faster and better COVID recovery.

In our study, vaccination against COVID-19 is associated with a lower risk of outcomes that 8 have not been assessed in previous studies, namely new-onset diseases including 9 hypertension, diabetes, malignant neoplasms, heart and thyroid diseases, 10 hypercoagulopathy or venous thromboembolism, and mental disorders, or new-onset 11 symptoms known to be part of long-COVID syndrome like headaches, fatigue, body aches, 12 and respiratory and gastrointestinal symptoms. We also found significant differences in 18) . However, we 2 hypothesize that its effect on reducing the inflammatory responses during the acute phase 3 does also explain the lower rates of all PASC outcomes observed in our study among the 4 vaccinated group.

Moreover, it should be noted that we very carefully captured new outcomes (eg. 6 Hypertension, cardiovascular disease, diabetes) that occurred after COVID infection and 7 not any pre-existing medical conditions. On that, COVID-19 has been associated with new- Apart from the above-mentioned lack of understanding in the pathophysiology of PASC, 20 detailing the predictors of it is also essential but still unknown. Only a few studies have 21 previously tackled the subject, with most of them revealing that long-term unfavorable

outcomes (ie PASC symptoms) were significantly more frequent in women, those with 1 longer hospital stays, those required ICU admissions, and those with higher symptom load 2 in the acute phase(23, 24). Furthermore, findings of another study suggest that moderate 3 and severe obesity (BMI ≥ 35 kg/m2) is associated with a greater risk of PASC. This 4 observation can be explained not only by the underlying mechanisms of obesity, including 5 obesity-related hyperinflammation, immune dysfunction, and co-morbidities, but also the Despite the novelty of our findings, our study has several limitations. First, the use of 17 electronic medical records to capture data. Second, the true prevalence of PASC among 18 COVID-19 patients is still unknown since many asymptomatic patients have never been 19 tested. Third, we cannot rule out the possibility that immunization status affects the 20 probability to seek or receive medical attention, particularly for less severe outcomes.

Fourth, this study is not informative on outcomes in patients infected with SARS-CoV-2 but 22 who did not get tested nor diagnosed with COVID-19. Additionally, our vaccination rate is

low and we cannot rule out that EMR documentation of vaccination may have been missed 1 some of the vaccinated individuals. Another potential limitation is that capturing the 2 location that patients were seen and the difference between health care utilization among 3 the two groups based on their concurrent comorbidities; which might provide another 4 potential explanation for the post-covid outcomes that we have described, is beyond the 5 capacity of this database. Finally, being an observational study, causation cannot be 6 inferred.

In summary, the present data show that prior vaccination against COVID-19, is associated 

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