Disaggregating the data: Diversity of COVID-19 stressors, discrimination, and mental health among Asian American communities

Much of the public discourse as well as research regarding the negative impact of COVID-19-related anti-Asian discrimination has been conducted at the broad racial group level, yet data aggregation masks critical points of diversity among Asian Americans. We conducted an online survey of 620 Asian American adults in December 2020 and examined whether there were any demographic differences–including by ethnic subgroup and Chinese street race (being Chinese or being mistaken as Chinese)–in their experiences of COVID-19-related stress, direct and vicarious discrimination, and psychological outcomes. Our analyses found that younger age was correlated with higher reports of pandemic stress, discrimination, distress, and worry. Female and U.S.-born participants reported higher levels of pandemic stress and vicarious discrimination, but there were no gender or nativity differences in levels of direct discrimination. Being uninsured was also related to higher levels of pandemic stress, discrimination, and distress. East Asian Americans reported significantly lower frequencies of direct anti-Asian discrimination than did South Asian or Southeast Asian Americans, but the ethnic subgroups did not differ in their reports of vicarious discrimination. Of note, Chinese street race was not associated with either direct or vicarious discrimination. Separate hierarchical regression analyses for East Asian, South Asian, and Southeast Asian participants revealed that, regardless of ethnicity, racial discrimination significantly contributed to psychological distress and worry beyond the effects of pandemic stress. However, the three groups varied in the demographic indicators and COVID-19 stressors that were associated with psychological outcomes. Pandemic stress was more strongly associated with negative outcomes among South Asian Americans than East Asian and Southeast Asian Americans, and neither direct nor vicarious discrimination were associated with mental health among South Asian Americans. Direct discrimination, compared to vicarious discrimination, was a particularly robust predictor of both distress and worry among East Asian Americans. For Southeast Asian Americans, direct discrimination significantly predicted higher levels of distress, whereas vicarious discrimination predicted higher levels of worry. Vicarious discrimination was not significantly related to distress across ethnic subgroups. Results suggest that practitioners and policy makers would benefit from attending to these within-group differences in Asian Americans' experiences during the pandemic.

SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity.

Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.

Prolonged SARS-CoV-2 Infection in Patients with Lymphoid Malignancies.

Coronavirus disease 2019 (COVID-19) infection results in both acute mortality and persistent and/or recurrent disease in patients with hematologic malignancies, but the drivers of persistent infection in this population are unknown. We found that B-cell lymphomas were at particularly high risk for persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. Further analysis of these patients identified discrete risk factors for initial disease severity compared with disease chronicity. Active therapy and diminished T-cell counts were drivers of acute mortality in COVID-19-infected patients with lymphoma. Conversely, B cell-depleting therapy was the primary driver of rehospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population. SIGNIFICANCE: We describe the largest cohort of persistent symptomatic COVID-19 infection in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.This article is highlighted in the In This Issue feature, p. 1.

Rotational thromboelastometry in patients with acute respiratory distress syndrome owing to coronavirus disease 2019: Is there a viscoelastic fingerprint and a role for predicting thrombosis?

OBJECTIVES: We evaluated rotational thromboelastometry tracings in 44 critically ill coronavirus disease 2019 patients, to determine whether there is a viscoelastic fingerprint and to test the hypothesis that the diagnosis and prediction of venous thromboembolism would be enhanced by the addition of rotational thromboelastometry testing. RESULTS: Rotational thromboelastometry values reflected an increase in clot strength for the EXTEM, INTEM, and FIBTEM assays beyond the reference range. No hyperfibrinolysis was noted. Fibrinolysis shutdown was present but did not correlate with thrombosis; 32% (14/44) of patients experienced a thrombotic episode. For every 1 mm increase of FIBTEM maximum clot formation, the odds of developing thrombosis increased 20% (95% confidence interval, 0-40%, P = .043), whereas for every 1,000 ng/mL increase in D-dimer, the odds of thrombosis increased by 70% (95% confidence interval, 20%-150%, P = .004), after adjustment for age and sex (AUC 0.96, 95% confidence interval, 0.90-1.00). There was a slight but significant improvement in model performance after adding FIBTEM maximum clot formation and EXTEM clot formation time to D-dimer in a multivariable model (P = .04). CONCLUSIONS: D-dimer concentrations were more predictive of thrombosis in our patient population than any other parameter. Rotational thromboelastometry confirmed the hypercoagulable state of coronavirus disease 2019 intensive care unit patients. FIBTEM maximum clot formation and EXTEM clot formation time increased the predictability for thrombosis compared with only using D-dimer. Rotational thromboelastometry analysis is most useful in augmenting the information provided by the D-dimer concentration for venous thromboembolism risk assessment when the D-dimer concentration is between 1,625 and 6,900 ng/dL, but the enhancement is modest. Fibrinolysis shutdown did not correlate with thrombosis.

Surgical oncology operative experience at a high-volume safety-net hospital during the COVID-19 pandemic.

BACKGROUND: The coronavirus (COVID-19) pandemic led to disruptions in operative and hospital capabilities as the country triaged resources and canceled elective procedures. This study details the operative experience of a safety-net hospital for cancer-related operations during a 3-month period at the height of the pandemic. METHODS: Patients operated on for or diagnosed with malignancies of the abdomen, breast, skin, or soft-tissue (September 3, 2020-September 6, 2020) were identified from operative/clinic schedules. Sociodemographics, tumor and treatment characteristics, and COVID-19 information was identified through retrospective chart review of a prospectively maintained database. Descriptive statistics were calculated. RESULTS: Fifty patients evaluated within this window underwent oncologic surgery. Median age was 61 (interquartile range: 53-68), 56% were female, 86% were White, and 66% were Hispanic. The majority (28%) were for colon cancer. Only two patients tested positive for COVID-19 preoperatively or within 30 days of their operation. There were no mortalities during the 1-year study period. CONCLUSION: During the COVID-19 pandemic, many hospitals and operative centers limited interventions to preserve resources, but oncologic procedures continued at many large-volume academic cancer centers. This study underscores the importance of continuing to offer surgery during the pandemic for surgical oncology cases at safety-net hospitals to minimize delays in time-sensitive oncologic treatment.

Systems serology detects functionally distinct coronavirus antibody features in children and elderly.

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.

Probative Value of the D-Dimer Assay for Diagnosis of Deep Venous Thrombosis in the Coronavirus Disease 2019 Syndrome.

OBJECTIVES: To describe the predictive utility of the D-dimer assay among patients with the coronavirus disease 2019 syndrome for unprovoked lower extremity deep venous thrombosis. DESIGN: Prospective observational study with retrospective data analysis. SETTING: Academic medical center surgical ICU. PATIENTS: Seventy-two intubated patients with critical illness from coronavirus disease 2019. INTERVENTIONS: Therapeutic anticoagulation after imaging diagnosis of the first three deep venous thrombosis cases was confirmed; therapeutic anticoagulation as prophylaxis thereafter to all subsequent ICU admissions. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients with severe coronavirus disease 2019 were screened for deep venous thrombosis after ICU admission with 102 duplex ultrasound examinations, with 12 cases (16.7%) of lower extremity deep venous thrombosis identified. There were no differences between groups with respect to age, renal function, or biomarkers except for D-dimer (median, 12,858 ng/mL [interquartile range, 3,176-30,770 ng/mL] for lower extremity deep venous thrombosis vs 2,087 ng/mL [interquartile range, 638-3,735 ng/mL] for no evidence of deep venous thrombosis; p < 0.0001). Clinical screening tools (Wells score and Dutch Primary Care Rule) had no utility. The C-statistic for D-dimer concentration was 0.874 ± 0.065. At the model-predicted cutoff value of 3,000 ng/mL, sensitivity was 100%, specificity was 51.1%, positive predictive value was 21.8%, and negative predictive value was 100%. CONCLUSIONS: Lower extremity deep venous thrombosis is prevalent in coronavirus disease 2019 disease and can be present on ICU admission. Screening has been recommended in the context of the pro-inflammatory, hypercoagulable background milieu. D-dimer concentrations are elevated in nearly all coronavirus disease 2019 patients, and the test appears reliable for screening for lower extremity deep venous thrombosis at or above a concentration of 3,000 ng/mL (more than 13-fold above the normal range). Full anticoagulation is indicated if the diagnosis is confirmed, and therapeutic anticoagulation should be considered for prophylaxis, as all coronavirus disease 2019 patients are at increased risk.

Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19.

Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

Acute upper limb ischemia as the first manifestation in a patient with COVID-19.

Coronavirus disease-19 (COVID-19) first emerged in December 2019 in China and rapidly spread worldwide. Although various studies have reported that COVID-19 is associated with a hypercoagulable state and thrombotic complications in critically ill patients, there are few case reports on thrombotic events as one of the presenting symptoms. We report a case of acute upper extremity ischemia as the initial clinical presentation of a patient with COVID-19.

Population-scale longitudinal mapping of COVID-19 symptoms, behaviour and testing.

Despite the widespread implementation of public health measures, coronavirus disease 2019 (COVID-19) continues to spread in the United States. To facilitate an agile response to the pandemic, we developed How We Feel, a web and mobile application that collects longitudinal self-reported survey responses on health, behaviour and demographics. Here, we report results from over 500,000 users in the United States from 2 April 2020 to 12 May 2020. We show that self-reported surveys can be used to build predictive models to identify likely COVID-19-positive individuals. We find evidence among our users for asymptomatic or presymptomatic presentation; show a variety of exposure, occupational and demographic risk factors for COVID-19 beyond symptoms; reveal factors for which users have been SARS-CoV-2 PCR tested; and highlight the temporal dynamics of symptoms and self-isolation behaviour. These results highlight the utility of collecting a diverse set of symptomatic, demographic, exposure and behavioural self-reported data to fight the COVID-19 pandemic.