{"id":4752,"date":"2022-06-12T15:54:51","date_gmt":"2022-06-12T15:54:51","guid":{"rendered":"http:\/\/wp.cov19longhaulfoundation.org\/?p=4752"},"modified":"2022-06-12T15:54:51","modified_gmt":"2022-06-12T15:54:51","slug":"risk-of-new%e2%80%90onset-psychiatric-sequelae-of-covid%e2%80%9019-in-the-early-and-late-post%e2%80%90acute-phase","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=4752","title":{"rendered":"Risk of new\u2010onset psychiatric sequelae of COVID\u201019 in the early and late post\u2010acute phase"},"content":{"rendered":"\n

Authors: Ben Coleman<\/a>, 1 , 2 <\/sup>Elena Casiraghi<\/a>, 3 , 4 <\/sup>Hannah Blau<\/a>, 1 <\/sup>Lauren Chan<\/a>, 5 <\/sup>Melissa A. Haendel<\/a>, 6 <\/sup>Bryan Laraway<\/a>, 6 <\/sup>Tiffany J. Callahan<\/a>, 6 <\/sup>Rachel R. Deer<\/a>, 7 <\/sup>Kenneth J. Wilkins<\/a>, 8 <\/sup>Justin Reese<\/a>, 9 <\/sup>and Peter N. Robinson<\/a> 1 , 2<\/sup> World Psychiatry.<\/a> 2022 Jun; 21(2): 319\u2013320 2022 May 7. doi: 10.1002\/wps.20992<\/a> PMCID: PMC9077621 PMID: 35524622<\/a><\/p>\n\n\n\n

Recent publications have documented that a proportion of COVID\u201019 patients develop psychiatric symptoms during or after acute infection 1 <\/a>. We investigated this risk in the context of the National COVID Cohort Collaborative (N3C) \u2013 a centralized, harmonized, high\u2010granularity electronic health record (EHR) repository 2 <\/a>\u2013 using the largest retrospective cohort reported to date.<\/p>\n\n\n\n

Two previous large\u2010scale EHR studies examined psychiatric sequelae 90 and 180 days after COVID\u201019 diagnosis. A cohort of 44,779 individuals with COVID\u201019 was propensity score\u2010matched to control cohorts with conditions such as influenza and other respiratory tract infections (RTI). In the 90 days following the initial presentation, the incidence proportion of new\u2010onset psychiatric conditions was 5.8% in the COVID\u201019 group vs. 2.5% to 3.4% in the control groups 3 <\/a>. A follow\u2010up study also included individuals with a prior history of mental illness and similarly showed an increased risk of psychiatric conditions in the six months following initial presentation 4 <\/a>.<\/p>\n\n\n\n

To validate these findings, we leveraged data from N3C, which at our cutoff date of October 20, 2021 had 1,834,913 COVID\u201019 positive patients and 5,006,352 comparable controls. Our data set was drawn from 51 distinct clinical organizations. We included patients in the COVID\u201019 cohort if they had a confirmed diagnosis of SARS\u2010CoV\u20102 infection by polymerase chain reaction or antigen test after January 1, 2020. Controls were selected from patients with a diagnosis of a RTI other than COVID\u201019. We excluded from this analysis patients with a history of any mental illness prior to 21 days after COVID\u201019 diagnosis, as well as patients without a medical record extending back a year prior to COVID\u201019. There were 245,027 COVID\u201019 positive individuals available for propensity matching.<\/p>\n\n\n\n

Each COVID\u201019 patient was matched with a control patient from the same institution whose age differed by no more than 5 years. Propensity score matching was done on 34 factors using a logistic regression model including main effect terms, resulting in 46,610 matched patient pairs. Multivariable Cox regression was performed to compare the incidence of new\u2010onset mental illness for all psychiatric conditions, mood disorders and anxiety disorders for 21 to 365 days following initial presentation. We additionally considered dyspnea as a positive control.<\/p>\n\n\n\n

We tested the Cox regression proportional hazard assumption for comparisons of COVID\u201019 patients and controls 5 <\/a>. Schoenfeld residual analysis yielded a significant p\u2010value and led us to reject the null hypothesis of a constant proportional hazard over the full time period of 21\u2010365 days. We therefore separated the cohort into two time intervals (before and after 120 days) in which the proportional hazard assumption was not violated.<\/p>\n\n\n\n

We identified a statistically significant difference in the hazard rate of new\u2010onset psychiatric sequelae between COVID\u201019 and RTI in the early post\u2010acute phase (from 21 to 120 days), but not in the late post\u2010acute phase (from 121 to 365 days). The estimated incidence proportion (as modeled on the log\u2010hazard scale over time) of a new\u2010onset psychiatric diagnosis in the early post\u2010acute phase for the COVID\u201019 group was 3.8% (95% CI: 3.6\u20104.0), significantly higher than the 3.0% (95% CI: 2.8\u20103.2) for the RTI group, with a hazard ratio (HR) of 1.3 (95% CI: 1.2\u20101.4). The HR for new\u2010onset mental illness in the late post\u2010acute phase was not significant in the COVID\u201019 compared to the RTI group (HR: 1.0; 95% CI: 0.97\u20101.1).<\/p>\n\n\n\n

Similar findings were obtained for anxiety disorders, but not for mood disorders. The estimated incidence proportion of a new\u2010onset anxiety disorder diagnosis was significantly increased for COVID\u201019 patients (2.0%; 95% CI: 1.8\u20102.1) compared to RTI patients (1.6%; 95% CI: 1.5\u20101.7) in the early post\u2010acute phase (HR: 1.3; 95% CI: 1.1\u20101.4). However, the estimated incidence proportion of a new\u2010onset mood disorder diagnosis in the same period was not significantly increased for COVID\u201019 patients (1.2%; 95% CI: 1.1\u20101.3) in comparison to RTI patients (1.1%; 95% CI: 1.0\u20101.2).<\/p>\n\n\n\n

New\u2010onset anxiety and mood disorders were not significantly increased in the interval of 121\u2010365 days following initial presentation (HR: 1.0, 95% CI: 0.91\u20101.1; and HR: 1.1, 95% CI: 0.97\u20101.2, respectively). In contrast, the HR for dyspnea, a known post\u2010acute COVID\u201019 sequela 1 <\/a>, increased in both time periods (1.4, 95% CI: 1.2\u20101.5; and 1.2, 95% CI: 1.0\u20101.3, respectively).<\/p>\n\n\n\n

We reasoned that patients might be followed more closely after COVID\u201019 as compared with other RTIs, and that a higher visit frequency might increase the probability of a mental illness being recorded in the EHR. To assess this, we repeated our analysis but added the frequency of visits 21 days or more after initial presentation as a factor to the Cox regression. The HR for any mental illness in the early post\u2010acute phase was still significant (p<0.0001), but reduced to 1.2 (95% CI: 1.1\u20101.3).<\/p>\n\n\n\n

Our results confirm the conclusion of the above\u2010cited study 3 <\/a>that patients are at significantly increased risk of psychiatric conditions after a COVID\u201019 diagnosis. However, the degree of increased risk documented in our study is substantially lower than previously found.<\/p>\n\n\n\n

There are several potential reasons for the differences between our results and those of the above\u2010mentioned study. The previous study included data from January 20, 2020 (first recorded COVID\u201019 case in the US) to August 1, 2020, while our study includes data through October 20, 2021. It is conceivable that perceptions of COVID\u201019 by patients have shifted or that clinical practice has changed in the intervening time. It is possible that improved treatment options available later in the pandemic have reduced the risk of psychiatric illness. Finally, COVID\u201019 vaccination may reduce rates of anxiety and depression and alleviate symptoms in persons with post\u2010acute sequelae 6 <\/a>, 7 <\/a>. Thus, the increasing availability of vaccines might have reduced the rate of mental illness following COVID\u201019. The data available in N3C do not include comprehensive information about vaccination status, so we could not test this hypothesis.<\/p>\n\n\n\n

Many cohort studies have documented a high prevalence of mental illness in individuals with long COVID. For instance, in our recent analysis, the prevalence of depression was 21.1% (median reported percentage in 25 studies) and that of anxiety was 22.2% (median over 24 studies) 1 <\/a>. However, it is possible that the reported prevalence of these and other conditions was in\u00adflated by a sampling bias toward long COVID patients who joined support groups or chose to participate in cohort studies 8 <\/a>. This, and the fact that inclusion criteria for long COVID studies vary, has made it difficult to characterize the natural history of psychiatric manifestations of long COVID. Our study did not fo\u00adcus specifically on long COVID, but instead investigated a cohort of patients following a diagnosis of acute COVID\u201019. It is difficult to know what proportion of these patients went on to develop long COVID; the recent introduction of ICD\u201010 codes for long COVID 9 <\/a>may enable studies on this topic in the future.<\/p>\n\n\n\n

In summary, we support previously published reports of an increased risk of new\u2010onset psychiatric illness following acute COVID\u201019 infection. In contrast to the nearly doubled risk identified by the earlier study, we found the relative risk to be increased by only about 25% (3.8% vs. 3.0% following other RTI). We did not find a significant difference in risk in the late post\u2010acute phase, suggesting that the increased risk of new\u2010onset psychiatric illness is concentrated in the early post\u2010acute phase.<\/p>\n\n\n\n

Our results have important implications for understanding the natural history of psychiatric manifestations of COVID\u201019. If confirmed by independent studies, our findings suggest that health services should consider mental health screening efforts early in the post\u2010COVID clinical course.<\/p>\n\n\n\n

Go to:<\/a><\/p>\n\n\n\n

NOTES<\/h2>\n\n\n\n

This work was supported by the US National Center for Advancing Translational Sciences (grant no. U24 TR002306).<\/p>\n\n\n\n

Go to:<\/a><\/p>\n\n\n\n

REFERENCES<\/h2>\n\n\n\n

1. Deer RR, Rock MA, Vasilevsky N et al. EBioMedicine<\/em> 2021;74:103722. [PMC free article<\/a>] [PubMed<\/a>] [Google Scholar<\/a>]<\/p>\n\n\n\n

2. Haendel MA, Chute CG, Bennett TD et al. J Am Med Inform Assoc<\/em> 2021;28:427\u201043. [PMC free article<\/a>] [PubMed<\/a>] [Google Scholar<\/a>]<\/p>\n\n\n\n

3. Taquet M, Luciano S, Geddes JR et al. Lancet Psychiatry<\/em> 2021;8:130\u201040. [PMC free article<\/a>] [PubMed<\/a>] [Google Scholar<\/a>]<\/p>\n\n\n\n

4. Taquet M, Geddes JR, Husain M et al. Lancet Psychiatry<\/em> 2021;8:416\u201027. [PMC free article<\/a>] [PubMed<\/a>] [Google Scholar<\/a>]<\/p>\n\n\n\n

5. Grambsch PM, Therneau TM. Biometrika<\/em> 1994;81:515. [Google Scholar<\/a>]<\/p>\n\n\n\n

6. Arnold DT, Milne A, Samms E et al. medRxiv<\/em> 2021;21253225. [Google Scholar<\/a>]<\/p>\n\n\n\n

7. Perez\u2010Arce F, Angrisani M, Bennett D et al. PLoS One<\/em> 2021;16:e0256406. [PMC free article<\/a>] [PubMed<\/a>] [Google Scholar<\/a>]<\/p>\n\n\n\n

8. Davis HE, Assaf GS, McCorkell L et al. EClinicalMedicine<\/em> 2021;38:101019. [PMC free article<\/a>] [PubMed<\/a>] [Google Scholar<\/a>]<\/p>\n\n\n\n

9. Duerlund LS, Shakar S, Nielsen H et al. Clin Epidemiol<\/em> 2022;14:141\u20108. [PMC free article<\/a>] [PubMed<\/a>] [Google Scholar<\/a>]<\/p>\n","protected":false},"excerpt":{"rendered":"

Authors: Ben Coleman, 1 , 2 Elena Casiraghi, 3 , 4 Hannah Blau, 1 Lauren Chan, 5 Melissa A. Haendel, 6 Bryan Laraway, 6 Tiffany J. Callahan, 6 Rachel R. Deer, 7 Kenneth J. Wilkins, 8 Justin Reese, 9 and Peter N. Robinson 1 , 2 World Psychiatry. 2022 Jun; 21(2): 319\u2013320 2022 May 7. doi: 10.1002\/wps.20992 PMCID: PMC9077621 […]<\/p>\n","protected":false},"author":2,"featured_media":4770,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[687,101,113,990,289,290],"tags":[],"class_list":["post-4752","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-anxiety","category-covid-19","category-depression-mental-health","category-dyspnea","category-long-haul-disease","category-long-term-effects"],"_links":{"self":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/4752","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=4752"}],"version-history":[{"count":0,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/4752\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/4770"}],"wp:attachment":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4752"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=4752"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=4752"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}