The clinicopathologic spectrum of dedifferentiated, undifferentiated, and transdifferentiated melanoma occurring de novo or following systemic therapy is gaining recognition. Here, we present a patient with locally advanced cutaneous melanoma who received neoadjuvant anti-PD-1 therapy and whose post-treatment excisional pathology revealed transdifferentiation into a ganglioneuroblastic phenotype. This rare phenotype is hypothesized to be connected to melanoma's shared origin from pluripotent neural crest cells. This case report highlights the proposed pathogenic mechanisms underlying this transition after immune checkpoint therapy, including the pathways and factors that affect the tumor and its microenvironment.

With the increasing utilization of telemedicine since the COVID-19 pandemic, it is critical that clinicians have an appropriate understanding of the application of virtual care resources, including teledermatology. We present a case series of 3 patients to demonstrate the clinical utility of teledermatology in reducing the time to diagnosis of various rare and/or aggressive cutaneous malignancies, including Merkel cell carcinoma, malignant melanoma, and atypical fibroxanthoma. Cases were obtained from one large Midwestern medical center during the month of July 2021. Each case presented includes a description of the initial teledermatology presentation and reviews the clinical timeline from initial consultation submission to in-person clinic visit with lesion biopsy. This case series demonstrates real-world examples of how teledermatology can be utilized to expedite the care of specific vulnerable patient populations.

Summary: Standard of care treatment for metastatic cutaneous adnexal carcinomas is not well established. In this case report, we highlight the successful use of anti–programmed cell death protein 1 (anti-PD-1) therapy in treating a patient with low tumor mutation burden, microsatellite stable, high programmed death-ligand 1 (PD-L1) gene expression, metastatic primary cutaneous adnexal carcinoma with significant radiographic, and circulating tumor DNA response with durable benefit. Immune checkpoint inhibitors hold promise as a future treatment option in rare instances of metastatic disease from primary skin adnexal carcinoma. Further studies are needed to identify better immune checkpoint inhibitor predictive biomarkers for rare, advanced-stage non-melanoma skin cancers.

Inequality has become a central concern in global discourse. This chapter delves into the relationship between economic freedom and inequality, aiming to enhance our understanding of this crucial issue. While capitalism is often accused of exacerbating inequality, the chapter explores the role of economic freedom as a defining aspect of capitalism and its potential influence on resource distribution. By reviewing empirical studies from peer-reviewed journals, the chapter examines multidimensional measures of economic freedom and their association with various forms of inequality, including income inequality, as well as disparities in happiness, health, and across gender and racial lines. The chapter also investigates specific aspects of economic freedom, such as private property rights, regulation, and privatization. By consolidating and analyzing existing research, this chapter contributes to the ongoing discourse on economic freedom, inequality, and policy measures aimed at reducing disparities.

INTRODUCTION:Fremanezumab is a humanized monoclonal antibody administered through a subcutaneous injection. It is used for treatment of migraines, and occasional injection site reactions have developed after usage.CASE PRESENTATION:This case report describes a nonimmediate injection site reaction on the right thigh of a 25-year-old female patient after starting treatment with fremanezumab. The injection site reaction presented as 2 warm, red annular plaques 8 days following a second injection of fremanezumab and about 5 weeks following the first injection. She was prescribed a 1-month course of prednisone that relieved her symptoms of redness, itching, and pain.DISCUSSION:Similar nonimmediate injection site reactions have been reported before, but this particular injection site reaction was significantly more delayed.CONCLUSIONS:Our case illustrates that injection site reactions to fremanezumab can be delayed after the second dose and may require systemic therapy to alleviate symptoms.

Pilomatricomas (PMs) are common benign adnexal tumors that show a predilection for the head and neck region and are characterized at the molecular level by activating mutations in the beta-catenin (CTNNB1) gene. Giant PMs are a rare histopathological variant, according to the World Health Organization, which are defined by a size greater than 4 cm and are reported to show upregulation of yes-associated protein compared to PMs of typical 1-3 cm size. We describe the case of a 67-year-old man with an 8 cm giant PM involving his temporal scalp, whose PM we characterized by 10X spatial gene expression analysis. This revealed five total transcriptomic clusters, including four distinct clusters within the giant PM, each with a unique transcriptional pattern of hair follicle-related factors, keratin gene expression, and beta-catenin pathway activity.

Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is the most common lymphoid malignancy in the Western world and classically presents as a rapidly enlarging nodal or extranodal mass. Cutaneous involvement by systemic DLBCL NOS is an infrequent clinical presentation, encountered in only 1.5-3.5% of cases, while disseminated cutaneous disease with multiple subcutaneous nodules at the time of diagnosis is unusual and can present a diagnostic challenge. The differential diagnosis when encountering a high-grade B-cell malignancy at a cutaneous site is broad and includes primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-MYC/BCL2), and other potential entities which must all be carefully considered before rendering a final diagnosis. In this report, we describe the case of a 69-year-old man who was seen at our hospital due to generalized weakness and was found to have multiple subcutaneous nodules representing disseminated DLBCL NOS. The case was complicated by concurrent monoclonal B-cell lymphocytosis involving the bone marrow.

Weinhammer, Annika MD*; Bennett, Daniel D. MD*; Eickhoff, Jens PhD†; Xu, Yaohui G. MD, PhD* Author Information

Generalized granuloma annulare (GA) is an uncommon form of GA that is recalcitrant to treatment.1In contrast to localized GA, the generalized form is characterized by widespread annular plaques or papules over the trunk and extremities.1 Although the lesions are frequently asymptomatic, the lesions can be disfiguring and decrease the patient’s quality of life. Therefore, extensive disease might justify more aggressive treatment. We report a patient with generalized GA resistant to conventional treatments who experienced dramatic improvement with oral vitamin E and topical tea tree oil (TTO).

This research provides an improved understanding of how ventures successfully organize via resource allocations. Conceptually, we apply elements of action theory to account for resource trade-offs that occur as entrepreneurs make decisions about adding staff members to boundary spanning, technical core, and management functions. We then model how these allocation decisions differentially impact nascent venture performance. Empirically, we test our model with a sample of 2484 entrepreneurs captured in the Kauffman Firm Survey, a longitudinal dataset that tracks a random sample of US startups over an 8-year period. Results from dynamic panel estimation reveal evidence of both performance penalties and performance boosts as the result of entrepreneurs adding staff to specific areas, revealing optimality in specific configurations of entrepreneurial organizing elements.

Background Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. Methods RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. Results For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gomori methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." Limitations: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. Conclusions AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

To the Editor: Mortality and metastatic rates of cutaneous squamous cell carcinoma (cSCC) correlate with tumor invasion1Schmults C.D. Karia P.S. Carter J.B. Han J. Qureshi A.A. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study.JAMA Dermatol. 2013; 149: 541-547Crossref PubMed Scopus (323) Google Scholar but current guidelines for measuring cSCC are inconsistent.2Amin M.B. Edge S. Greene F. AJCC. Cancer Staging Manual. 8th ed. Springer, 2017Crossref Google Scholar, 3Protocol for the examination of specimens from patients with carcinomas of the skin. Squamous cell carcinoma of the skin. Version 3.1.0.2. College of American Pathologists.https://webapps.cap.org/apps/docs/committees/cancer/cancer_protocols/2013/SkinSquamous_13protocol_3102.pdfDate accessed: October 11, 2021Google Scholar, 4Eigentler T.K. Leiter U. Häfner H.M. Garbe C. Röcken M. Breuninger H. Survival of patients with cutaneous squamous cell carcinoma: results of a prospective cohort study.J Invest Dermatol. 2017; 137: 2309-2315Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar The eighth American Joint Committee Cancer recommends measuring from the top of the adjacent normal epidermis, or “shoulder” of the tumor, to the base.2Amin M.B. Edge S. Greene F. AJCC. Cancer Staging Manual. 8th ed. Springer, 2017Crossref Google Scholar The College of American Pathologists recommends measuring at a right angle from overlying or adjacent normal epidermis to the tumor base, or from the ulcer base to the tumor base if the cSCC is completely ulcerated.3Protocol for the examination of specimens from patients with carcinomas of the skin. Squamous cell carcinoma of the skin. Version 3.1.0.2. College of American Pathologists.https://webapps.cap.org/apps/docs/committees/cancer/cancer_protocols/2013/SkinSquamous_13protocol_3102.pdfDate accessed: October 11, 2021Google Scholar It has been shown (T. Eigentler and H. Breuninger, personal communication, December 2017) that cSCC thickness correlated with tumor-specific death,4Eigentler T.K. Leiter U. Häfner H.M. Garbe C. Röcken M. Breuninger H. Survival of patients with cutaneous squamous cell carcinoma: results of a prospective cohort study.J Invest Dermatol. 2017; 137: 2309-2315Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar measuring from the highest part of the tumor, or the shoulder in an ulcerated tumor, to the deepest tumor cells. Breslow thickness is precise and has been validated as an independent prognostic factor for melanoma. Pathologists typically measure the thickest component from the top of the granular layer (or from the base of the ulcer if the ulcer is above the thickest component) to the deepest part immediately beneath.5Elder D.E. Lever's Histopathology of the Skin. 11th ed. Wolters Kluwer, 2015Google Scholar We propose to standardize the measurement of cSCC thickness utilizing Breslow technique to provide accurate and consistent staging of cSCC. We performed an institutional review board (University of Wisconsin School of Medicine and Public Health, Madison, WI) –approved prospective case series of patients presenting for Mohs micrographic surgery for treatment of cSCC with high-risk features (clinically >2 cm, poor differentiation, and/or perineural invasion). Permanent section histology slides of 29 central debulk specimens were reviewed by dermatopathologists (DDB, BJL) and Mohs surgeon (YGX). One case was excluded because no residual tumor was identified. Twenty-eight cases were measured for tissue-level invasion and millimeter thickness using the eighth American Joint Committee Cancer, College of American Pathologists, and Breslow techniques. Seventeen (60.7%) of 28 cases showed a discrepancy in millimeter thickness among the 3 techniques (Table I). Twelve (42.9%) of 28 cases differed when measuring from the shoulder versus Breslow thickness. Seven (25%) of 28 cases differed from the shoulder versus the ulcer base. In 7 (25%) of 28 cases, the discrepancy could affect staging (crossed 6 mm). The inter-/intra-rater discrepancy was substantial, with a large coefficient of variation value of 1.03 for the absolute differences between raters and a median value of 0.5 mm (range, 0-2.5 mm; P < .0001). Discrepancies were exaggerated for exophytic and/or endo-exophytic tumors (Fig 1; Supplementary Fig 1, available via Mendeley at https://doi.org/10.17632/ch6hbh6ybs.1). Two (7.1%) of 28 patients had recurrence with metastases to regional lymph nodes (patients 13 and 16).Table ICutaneous squamous cell carcinoma thickness measurements utilizing current measurement techniques and a measurement that mimics Breslow thickness of melanomaCaseThickness (mm) from granular layer of adjacent normal skin (“shoulder”)∗The shoulder is defined as the top of the granular layer of the adjacent normal epidermis.(AJCC 8th and CAP)Thickness (mm) from base of ulcer†The ulcer base is considered the lowest portion of the ulcerated/eroded surface.(CAP)Identical to melanoma Breslow thickness‡Breslow thickness of melanoma is measured from the top of the granular layer (or ulcer base if it gives the thickest measurement) to the deepest part immediately beneath.Discrepancy in mm (base of ulcer vs “shoulder”)Discrepancy in mm (Breslow thickness vs “shoulder”)Discrepancy in mm crossed 6 mm thresholdTissue-level invasion (AJCC 8th and BWH)¶Tissue-level invasion provides essential information that can be discordant from millimeter thickness. Of the 9 tumors that extended beyond subcutaneous fat and qualified as deep invasion per staging systems, 3 were less than 6 mm in thickness when utilizing the melanoma Breslow technique (cases 4, 11, and 23). There were 11 cases in which tumor thickness was over 6 mm when utilizing the melanoma Breslow technique but tissue-level invasion was not beyond subcutaneous fat (cases 5-8, 12, 13, 16, 22, 24, 25, and 27).Inter- and intraobserver discrepancy in mm measured from the shoulder (absolute difference = rater 1 vs rater 2)#When measuring from the shoulder, the inter-/intra-rater discrepancy was substantial with a large coefficient of variation value of 1.03 for the absolute differences between raters and a median value of 0.5 mm (range, 0-2.5 mm; P < .0001).Inter- and intraobserver discrepancy in mm measured as Breslow thickness (absolute difference = rater 1 vs rater 2)When measuring using Breslow technique, the inter-/intra-rater discrepancy was much smaller, with a median absolute difference of 0 mm (range, 0-0.5 mm; P = .004). One contributing factor to the interobserver variability was that some large squamous cell carcinoma specimens were beyond 1 low-power microscopic view to be measured as an entire specimen.18.3 mmN/A8.3 mmN/A0 mmNoMuscle1.2 mm (8.3 vs 9.5)0.1 mm (8.3 vs 8.4)25.7 mm5.5 mm5.7 mm0.2 mm0 mmNoSubcutaneous0 mm (5.7 vs 5.7)0 mm (5.7 vs 5.7)34.2 mm4.2 mm4.2 mm0 mm0 mmNoSubcutaneous1.7 mm (4.2 vs 2.5)0 mm (4.2 vs 4.2)40.7 mmN/A4.1 mmN/A3.4 mmNoMuscle1.2 mm (0.7 vs 1.9)0 mm (4.1 vs 4.1)51.3 mmN/A6.2 mmN/A4.9 mmYesDermis0.2 mm (1.3 vs 1.1)0.2 mm (6.2 vs 6.4)67.7 mm7.4 mm7.7 mm0.3 mm0 mmNoSubcutaneous0.3 mm (7.7 vs 8)0 mm (7.7 vs 7.7)75.6 mmN/A7.4 mmN/A1.8 mmYesSubcutaneous1.2 mm (5.6 vs 6.8)0 mm (7.4 vs 7.4)82.1 mmN/A6.1 mmN/A4.0 mmYesSubcutaneous2.5 mm (2.1 vs 4.6)0 mm (6.1 vs 6.1)93.0 mmN/A3.8 mmN/A0.8 mmNoDermis0.2 mm (3.0 vs 3.2)0.2 mm (3.8 vs 4.0)106.6 mmN/A§Squamous cell carcinoma not connected to epidermis; no ulcer or exophytic growth so only 1 number for depth measured.6.6 mmN/A§Squamous cell carcinoma not connected to epidermis; no ulcer or exophytic growth so only 1 number for depth measured.0 mmNoMuscle0 mm (6.6 vs 6.6)0 mm (6.6 vs 6.6)115.1 mm5.1 mm5.1 mm0 mm0 mmNoMuscle0.3 mm (5.1 vs 4.8)0.1 mm (5.1 vs 5.0)120.5 mmN/A6.6 mmN/A6.1 mmYesSubcutaneous1.9 mm (0.5 vs 2.4)0.2 mm (6.6 vs 6.8)134.5 mmN/A6.1 mmN/A1.6 mmYesSubcutaneous0.3 mm (4.5 vs 4.8)0 mm (6.1 vs 6.1)1411.8 mmN/A§Squamous cell carcinoma not connected to epidermis; no ulcer or exophytic growth so only 1 number for depth measured.11.8 mmN/A§Squamous cell carcinoma not connected to epidermis; no ulcer or exophytic growth so only 1 number for depth measured.0 mmNoMuscle0.3 mm (11.8 vs 11.5)0 mm (11.8 vs 11.8)152.9 mmN/A4.0 mmN/A1.1 mmNoSubcutaneous0.7 mm (2.9 vs 3.6)0 mm (4.0 vs 4.0)165.3 mmN/A11.3 mmN/A6 mmYesSubcutaneous2.3 mm (5.3 vs 3.0)0.2 mm (11.3 vs 11.5)173.4 mm3.4 mm3.4 mm0 mm0 mmNoSubcutaneous0.5 mm (3.4 vs 3.9)0 mm (3.4 vs 3.4)18N/A‖Unable to define shoulder of the tumor.N/A4.6 mmN/AN/A‖Unable to define shoulder of the tumor.NoDermisN/A‖Unable to define shoulder of the tumor.N/A‖Unable to define shoulder of the tumor.199.0 mm9.0 mm9.0 mm0 mm0 mmNoMuscle0.3 mm (9.0 vs 9.3)0 mm (9.0 vs 9.0)201.7 mm1 mm1.7 mm0.7 mm0 mmNoDermis0.2 mm (1.7 vs 1.5)0 mm (1.7 vs 1.7)218.1 mm7 mm8.1 mm1.1 mm0 mmNoMuscle1.9 mm (8.1 vs 10)0 mm (8.1 vs 8.1)226.5 mmN/A9.0 mmN/A2.5 mmNoSubcutaneous0.5 mm (6.5 vs 7.0)0.5 mm (9.0 vs 9.5)233.6 mm3.6 mm3.6 mm0 mm0 mmNoMuscle0 mm (3.6 vs 3.6)0 mm (3.6 vs 3.6)247.5 mmN/A7.5 mmN/A0 mmNoSubcutaneous0 mm (7.5 vs 7.5)0 mm (7.5 vs 7.5)259.0 mm8.1 mm9.0 mm0.9 mm0 mmNoSubcutaneous1 mm (9.0 vs 10.0)0.5 mm (9.0 vs 9.5)264.9 mm4.3 mm6.2 mm0.6 mm1.3 mmYesMuscle0.8 mm (4.9 vs 5.7)0 mm (6.2 vs 6.2)276.2 mmN/A6.2 mmN/A0 mmNoSubcutaneous0 mm (6.2 vs 6.2)0 mm (6.2 vs 6.2)282.9 mm3.6 mm4.2 mm0.7 mm1.3 mmNoDermis0.5 mm (2.9 vs 2.4)0.3 mm (4.2 vs 4.5)Millimeter thickness as well as tissue-level invasion of cutaneous squamous cell carcinoma measured from central tumor debulk specimens obtained prior to Mohs micrographic surgery and submitted for routine permanent section histology in 28 patients recruited from March 2016 to March 2020.AJCC 8th, The 8th American Joint Committee Cancer system; BWH, The Brigham and Women's Hospital staging system; CAP, College of American Pathologists; N/A, not applicable; subcutaneous, subcutaneous fat.∗ The shoulder is defined as the top of the granular layer of the adjacent normal epidermis.† The ulcer base is considered the lowest portion of the ulcerated/eroded surface.‡ Breslow thickness of melanoma is measured from the top of the granular layer (or ulcer base if it gives the thickest measurement) to the deepest part immediately beneath.§ Squamous cell carcinoma not connected to epidermis; no ulcer or exophytic growth so only 1 number for depth measured.‖ Unable to define shoulder of the tumor.¶ Tissue-level invasion provides essential information that can be discordant from millimeter thickness. Of the 9 tumors that extended beyond subcutaneous fat and qualified as deep invasion per staging systems, 3 were less than 6 mm in thickness when utilizing the melanoma Breslow technique (cases 4, 11, and 23). There were 11 cases in which tumor thickness was over 6 mm when utilizing the melanoma Breslow technique but tissue-level invasion was not beyond subcutaneous fat (cases 5-8, 12, 13, 16, 22, 24, 25, and 27).# When measuring from the shoulder, the inter-/intra-rater discrepancy was substantial with a large coefficient of variation value of 1.03 for the absolute differences between raters and a median value of 0.5 mm (range, 0-2.5 mm; P < .0001).∗∗ When measuring using Breslow technique, the inter-/intra-rater discrepancy was much smaller, with a median absolute difference of 0 mm (range, 0-0.5 mm; P = .004). One contributing factor to the interobserver variability was that some large squamous cell carcinoma specimens were beyond 1 low-power microscopic view to be measured as an entire specimen. Open table in a new tab Millimeter thickness as well as tissue-level invasion of cutaneous squamous cell carcinoma measured from central tumor debulk specimens obtained prior to Mohs micrographic surgery and submitted for routine permanent section histology in 28 patients recruited from March 2016 to March 2020. AJCC 8th, The 8th American Joint Committee Cancer system; BWH, The Brigham and Women's Hospital staging system; CAP, College of American Pathologists; N/A, not applicable; subcutaneous, subcutaneous fat. Our data underscore critical inconsistencies in current guidelines for measuring cSCC thickness. Most noticeably, using the granular layer of the adjacent normal epidermis (“shoulder”) for a tumor that is exophytic or endo-exophytic can generate strikingly inconsistent intra- and interobserver results. Fig 1 also illustrates that the measurement from the shoulder may result in understaging aggressive and thick tumors. Adapting Breslow technique for cSCC eliminates the variability and subjectivity in finding the shoulder, as all pathologists and dermatopathologists are trained to measure Breslow thickness accurately, allowing for rapid adaptation and consistent reporting. Future prospective studies are necessary to establish Breslow thickness as an independent prognostic indicator for cSCC. However, we propose that cSCC thickness should be measured using Breslow thickness, as is melanoma, to provide a common, precise, and reproducible measuring system. None disclosed. We appreciate support from the American Society for Dermatologic Surgery (2015 Cutting Edge Research Grant award to Dr Xu). We thank the research administrative team at the Department of Dermatology, University of Wisconsin at Madison, for their assistance. We thank Gerald Keyser, our Mohs histotechnician, for taking photomicrographs. We thank the University of Wisconsin at Madison, Institute for Clinical and Translational Research for providing a mechanism for statistical support.

To the Editor: We define “special actinic keratoses (AKs)” by 2 criteria: (1) location on anatomically sensitive sites that are cosmetically important (face) or tight skin (scalp, hands, feet, or lower legs) and (2) partial biopsy showing a complex AK extending to the base of the biopsy specimen without exclusion of carcinoma. Destructive treatments do not allow evaluation of underlying carcinoma. For AKs in esthetically sensitive locations, a vertically sectioned deeper biopsy/excision may generate a defect that requires a complex repair to avoid distortion of a free margin.

A high index of suspicion for incontinentia pigmenti should be maintained in neonatal vesicular eruptions of unclear etiology, especially in the setting of unexplained seizures and/or abnormal brain imaging.

Background The COVID-19 pandemic brought about large increases in mental distress. The uptake of COVID-19 vaccines is expected to significantly reduce health risks, improve economic and social outcomes, with potential benefits to mental health. Purpose To examine short-term changes in mental distress following the receipt of the first dose of the COVID-19 vaccine. Methods Participants included 8,003 adults from the address-based sampled, nationally representative Understanding America Study (UAS), surveyed at regular intervals between March 10, 2020, and March 31, 2021 who completed at least two waves of the survey. Respondents answered questions about COVID-19 vaccine status and self-reported mental distress as measured with the four-item Patient Health Questionnaire (PHQ-4). Fixed-effects regression models were used to identify the change in PHQ-4 scores and categorical indicators of mental distress resulting from the application of the first dose of the COVID-19 vaccine. Results People who were vaccinated between December 2020 and March 2021 reported decreased mental distress levels in the surveys conducted after receiving the first dose. The fixed-effects estimates show an average effect of receiving the vaccine equivalent to 4% of the standard deviation of PHQ-4 scores (p-value<0.01), a reduction in 1 percentage point (4% reduction from the baseline level) in the probability of being at least mildly depressed, and of 0.7 percentage points (15% reduction from the baseline level) in the probability of being severely depressed (p-value = 0.06). Conclusions Getting the first dose of COVID-19 resulted in significant improvements in mental health, beyond improvements already achieved since mental distress peaked in the spring of 2020.

The COVID-19 pandemic substantially changed daily life in ways that may impact mental health. This study compared a nationally representative online sample of 2,032 U.S. adults in late April 2020 to 19,330 U.S. adult internet users who participated in the 2018 National Health Interview Survey (NHIS) using the Kessler-6 scale of mental distress in the last 30 days. Compared to the 2018 NHIS sample, U.S. adults in April 2020 were eight times more likely to fit criteria for serious mental illness (27.7% vs. 3.4%) and three times more likely to fit criteria for moderate or serious mental illness (70.4% vs. 22.0%). Differences between the 2018 and 2020 samples appeared across all demographic groups, with larger differences among younger adults and those with children in the household. These considerable levels of mental distress may portend substantial increases in diagnosed mental disorders and in the morbidity and mortality associated with them.