Association of mRNA COVID-19 vaccination and reductions in Post-COVID Conditions […] in a US prospective cohort of essential workers, 2024, Mak+

SNT Gatchaman

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Association of mRNA COVID-19 vaccination and reductions in Post-COVID Conditions following SARS-CoV-2 infection in a US prospective cohort of essential workers
Mak, Josephine; Khan, Sana; Britton, Amadea; Rose, Spencer; Gwynn, Lisa; Ellingson, Katherine D; Meece, Jennifer; Feldstein, Leora; Tyner, Harmony; Edwards, Laura; Thiese, Matthew S; Naleway, Allison; Gaglani, Manjusha; Solle, Natasha; Burgess, Jefferey L; Lamberte, Julie Mayo; Shea, Meghan; Hunt-Smith, Taryn; Caban-Martinez, Alberto; Porter, Cynthia; Wiegand, Ryan; Rai, Ramona; Hegmann, Kurt T; Hollister, James; Fowlkes, Ashley; Wesley, Meredith; Philips, Andrew L; Rivers, Patrick; Bloodworth, Robin; Newes-Adeyi, Gabriella; Olsho, Lauren E W; Yoon, Sarang K; Saydah, Sharon; Lutrick, Karen

BACKGROUND
While there is evidence that COVID-19 vaccination protects against development of post-COVID conditions (PCC) after severe infection data are limited on whether vaccination reduces the risk after cases of less-severe non-hospitalized COVID-19 disease with more recent SARS-CoV-2 variant viruses. This study assessed whether COVID-19 vaccination was protective against subsequent development of PCC in persons with predominantly mild initial infections during both Delta and Omicron variant predominance.

METHODS
This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with PCR-confirmed SARS-CoV-2 infection between 6/28/2021 and 9/14/2022 were surveyed for PCC, defined by symptoms lasting >1 month after initial infection Cases were participants self-reporting PCC and controls were participants that did not self-report PCC. The exposure was mRNA COVID-19 vaccination (2 or 3 monovalent doses) versus no COVID-19 vaccination. Logistic regression was used to compare the odds of PCC among vaccinated and unvaccinated persons; additional analyses evaluating PCC subtypes were also performed.

RESULTS
A total of 936 participants with documented SARS-CoV-2 infection were included; of these 23.6% (221) reported PCC and 83.3% (779) were vaccinated. Participants who received a 3 rd COVID-19 monovalent mRNA dose prior to infection had lower odds of PCC-related gastrointestinal, neurological, and other symptoms compared to unvaccinated participants (aOR: 0.37; 95% CI: 0.16-0.85; aOR: 0.56; 95% CI: 0.32-0.97; aOR:0.48; 95% CI: 0.25-0.91).

CONCLUSIONS
COVID-19 vaccination protected against development of PCC among persons with mild infection during both Delta and Omicron variant predominance, supporting vaccination as an important tool for PCC prevention.

Link | PDF (The Journal of Infectious Diseases) [Open Access]
 
the HEROES-RECOVER cohort is unique in that it consists of predominantly younger, healthy adult participants and almost all infections captured represented non-severe disease. In total, approximately 25% of participants included in the analysis had 3 or fewer symptoms during their initial infection, 8.7% were asymptomatic, and only 6 of 936 (0.6%) had a hospitalization related to their infection.

This analysis found that 3 doses of an mRNA COVID-19 vaccine was associated with lower odds of experiencing specific categories of PCC symptoms following infection, including reducing the odds of other symptoms (weight loss, hair loss, skin, menstrual, and sexual symptoms) by 52%, gastrointestinal symptoms by 63%, and neurological symptoms by 44%.
 
Yeah, just a tad cringe! I looked it up: "Healthcare, Emergency Response and Other Essential Workers Surveillance Study".
 
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The HEROES-RECOVER network consists of two jointly run prospective cohorts: the Arizona Healthcare, Emergency Response, and Other Essential Workers Surveillance Study (HEROES) and Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER).18,19

The network began data collection in July 2020 and followed participants weekly through April 2023 for HEROES and May 2023 for RECOVER to collect exposure and infection information.
Just an unfortunate pairing of words I think on the HEROES-RECOVER issue - two separate cohorts.
 
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The analysis excluded participants with a history of SARS-CoV-2 infection prior to study enrollment (determined through self-report at enrollment or evidence of infection- induced SARS-CoV-2 antibodies on enrollment blood draw).

So, the study can't answer the question of whether previous infections alter the risk of persistent symptoms.
 
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Outcomes
The outcome of interest was PCC, defined as self-reported symptoms persisting four or more weeks after acute infection on self-report during survey. Cases were defined as participants who reported at least one symptom persisting for a month or longer when asked “Since your COVID- 19 illness .... have you had any of the below symptoms lasting over 4 consecutive weeks?”. Controls were defined as those who completed the PCC survey and did not report at least one symptom persisting for a month or longer. The full list of symptoms defining PCC is provided (Supplemental Table 1).

Symptoms could have been continuous since initial infection or relapsing/remitting since initial infection. PCC was further sub-categorized by number of symptoms ( ≥ one or ≥ two) and by symptom category: cardiovascular/respiratory (shortness of breath, palpitations, chest pain/tightness, and runny nose/congestion), gastrointestinal (loss of appetite, nausea, vomiting, abdominal/stomach pain, constipation, and diarrhea) , general (worsening of symptoms following minor mental or physical activity, fatigue, joint pain, joint swelling, and muscle pain), neurological (dizziness/lightheadedness/fainting, numbness/tingling, fogginess in thinking, change in sleeping, headache,difficultyspeaking/communicating, difficulty swallowing/chewing, problems with balance/movement), and other (weight loss, hair loss, change in color of toes/fingers, rash, bruising/bleeding easily, change in menstrual cycle, change in sexual drive, and erectile dysfunction).

It isn't clear to me how someone who had one or more persistent symptoms prior to the Covid-19 infection would have been dealt with in this study. I don't see anything about excluding them, or asking for only persistent symptoms that are new.

Overall, 215 (23.3%) participants reported experiencing ≥ one PCC symptom, with 152 (16.5%) reporting ≥2 symptoms. Of these 158 (71.5%) were female, 139 (62.9%) self-rated their enrollment health as “Excellent” or “Very Good”, and 126 (57.0%) self-reported using one or more physician- prescribed daily medications at enrollment. The most reported category of symptoms was general symptoms includ ing pain/fatigue (16.2%), followed by neurological (13.7%), cardiovascular/respiratory (11.4%), and other (8.5%); gastrointestinal symptoms were least common (4.9%) (Table 3). Persons reporting PCC symptoms compared with those who did not report PCC were more frequently symptomatic during acute infection (96.4% vs. 86.6%, p<0.001). Those who report PCC symptoms also more frequently reported >3 symptoms during acute infection compared to individuals who did not report PCC symptoms (82.8% vs. 69.4%, p<0.001, respectively) (Table 1).
 
Afteradjustment for gender, age, number of chronic conditions, number of symptoms during acute infection, interval between infection and survey completion, and variant type, and stratified by symptom category, receipt of 3 doses of vaccine was associated with lower odds of PCC gastrointestinal symptoms (aOR: 0.37; 95% CI: 0.16-0.85), neurological symptoms (aOR: 0.56; 95% CI: 0.32 – 0.97) and other symptoms (aOR: 0.48; 95% CI: 0.25 – 0.91) compared to being unvaccinated (Table 3). No significant associations were found between 3 doses of vaccine and the odds of number of symptoms, cardiovascular/respiratory symptoms, and general symptoms (Table 3).

Comparing receipt of two doses >=14 days prior to acute infection to unvaccinated, the odds of PCC with at least one symptom was 0.84 (95% CI = 0.53 – 1.32). The point estimate was lower compared to unvaccinated but not statistically significant. Assessing specific PCC symptom categories, the odds of cardiovascular/respiratory symptoms (aOR: 1.12; 95% CI= 0.62 – 2.05), gastrointestinal symptoms (aOR: 0.69; 95% CI = 0.31 – 1.53), general symptoms (aOR: 1.08; 95% CI=0.64 – 1.84), neurological symptoms (aOR: 0.80; 95% CI = 0.46 – 1.40), and other symptoms (aOR: 0.77; 95% CI =0.41 – 1.46)(Table 3).

This analysis found that 3 doses of an mRNA COVID-19 vaccine was associated with lower odds of experiencing specific categories of PCC symptoms following infection, including reducing the odds of other symptoms (weight loss, hair loss, skin, menstrual, and sexual symptoms) by 52%, gastrointestinal symptoms by 63%, and neurological symptoms by 44%. The differential effect on the development of PCC symptoms has been identified elsewhere in the literature. for example, in a recent meta-analysis, Gao, Liu, and Liu et al. identified vaccination to only be protective against some, but not all PCC symptoms.14

There was no association observed between development of PCC and receipt of 2 or 3 doses of mRNA COVID-19 vaccine. This is in contrast to other studies that have demonstrated a protective effect from 2 doses, including in similar cohorts of non-severe COVID-19 infections in the UK and in Italy.21,22 However, the median time between receipt of a second vaccine dose and acute infection was 324 days in the HEROES-RECOVER cohort. It is therefore possible the lack of an association observed here is the result of waning vaccine protection against development of PCC after infection similar to what is observed against infection itself; smaller sample size in the 2-dose group may also have played a role, limiting power to detect an association. Although further research is needed, the potential that protection against development of PCC after infection may ACCEPTED MANUSCRIPT wane just as it does for other outcomes highlights the importance of staying up to date with COVID-19 vaccination recommendations including updated doses.
 
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