POST-ACUTE SEQUELAE AND ADAPTIVE IMMUNE RESPONSES IN PEOPLE LIVING WITH HIV RECOVERING FROM SARS-COV-2 INFECTION

BackgroundLimited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH). MethodsWe measured SARS-CoV-2 specific humoral and cellular responses in people with and without HIV recovering from COVID-19 (n=39 and n=43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing post-acute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T cell responses, as well as differences in the prevalence of PASC. ResultsAmong PWH, we found broadly similar SARS-CoV-2-specific antibody and T cell responses as compared with a well-matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2 specific memory CD8+ T cells (p=0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2 specific CD4+ T cells (p=0.007). Higher CD4/CD8 ratio was associated with lower PD-1 expression on SARS-CoV-2 specific CD8+ T cells (0.34-fold effect, p=0.02). HIV status was strongly associated with PASC (odds ratio 4.01, p=0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms. ConclusionsWe identified potentially important differences in SARS-CoV-2 specific CD4+ and CD8+ T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

Details of COVID-19 Disease Mitigation Strategies in 17 K-12 Schools in Wood County, Wisconsin

ImportanceWith the current COVID-19 return-to-school guidelines, over half of Americas K-12 students are being denied access to full time in-person education, leading to harmful academic, emotional and health consequences. ObjectiveTo describe the specific details of mitigation strategies employed at 17 K-12 schools in Wisconsin during a time of exceptionally high COVID-19 community disease prevalence where in-school transmission was minimal. The aim of this report is to assist school districts and governing bodies in developing full-time return to school plans. DesignRetrospective cohort SettingWood County, Wisconsin, August 31-November 29, 2020 Participants5,530 students and staff from 17 schools in 4 school districts Main outcomes and measuresO_LIDistancing between primary and secondary students in school C_LIO_LISchool ventilation details C_LIO_LIMasking among teachers C_LIO_LILunch, recess and bussing practices C_LI Results89.3% of elementary students included in our study did not maintain 6 feet of physical distancing in the classroom and 94.8% were within 6 feet in lunchrooms. The majority of secondary students (86.2%) were able to maintain 6 feet of distancing in the classroom but no students were greater than 6 feet in the hallways. 58.8% of schools did not install new ventilation systems prior to the school year. Students ate lunch indoors. Bussing of students continued and all elementary children were allowed to go without masks at recess. Conclusion and relevanceIn the setting of high community COVID-19 disease transmission, 6 feet of distance between elementary students and major ventilation system renovations in primary or secondary schools do not appear to be necessary to minimize disease spread. Requiring masks at recess and prohibiting bussing also appears unnecessary. These findings may inform guidance on the safe reopening of schools and allow for more children to return to in-person schooling.

Rapid implementation of a cohort for the study of post-acute sequelae of SARS-CoV-2 infection/COVID-19

BACKGROUNDAs the coronavirus disease 2019 (COVID-19) pandemic continues and millions remain vulnerable to infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), attention has turned to characterizing post-acute sequelae of SARS-CoV-2 infection (PASC). METHODSFrom April 21 to December 31, 2020, we assembled a cohort of consecutive volunteers who a) had documented history of SARS-CoV-2 RNA-positivity; b) were [≥] 2 weeks past onset of COVID-19 symptoms or, if asymptomatic, first test for SARS-CoV-2; and c) were able to travel to our site in San Francisco. Participants learned about the study by being identified on medical center-based registries and being notified or by responding to advertisements. At 4-month intervals, we asked participants about physical symptoms that were new or worse compared to the period prior to COVID-19, mental health symptoms and quality of life. We described 4 time periods: 1) acute illness (0-3 weeks), 2) early recovery (3-10 weeks), 3) late recovery 1 (12-20 weeks), and 4) late recovery 2 (28-36 weeks). Blood and oral specimens were collected at each visit. RESULTSWe have, to date, enrolled 179 adults. During acute SARS-CoV-2 infection, 10 had been asymptomatic, 125 symptomatic but not hospitalized, and 44 symptomatic and hospitalized. In the acute phase, the most common symptoms were fatigue, fever, myalgia, cough and anosmia/dysgeusia. During the post-acute phase, fatigue, shortness of breath, concentration problems, headaches, trouble sleeping and anosmia/dysgeusia were the most commonly reported symptoms, but a variety of others were endorsed by at least some participants. Some experienced symptoms of depression, anxiety, and post-traumatic stress, as well as difficulties with ambulation and performance of usual activities. The median visual analogue scale value rating of general health was lower at 4 and 8 months (80, interquartile range [IQR]: 70-90; and 80, IQR 75-90) compared to prior to COVID-19 (85; IQR 75-90). Biospecimens were collected at nearly 600 participant-visits. CONCLUSIONAmong a cohort of participants enrolled in the post-acute phase of SARS-CoV-2 infection, we found many with persistent physical symptoms through 8 months following onset of COVID-19 with an impact on self-rated overall health. The presence of participants with and without symptoms and ample biological specimens will facilitate study of PASC pathogenesis. Similar evaluations in a population-representative sample will be needed to estimate the population-level prevalence of PASC.

Characterizing the COVID-19 illness experience to inform the study of post-acute sequalae and recovery: a qualitative study

We aimed to characterize the variability in the illness experience and recovery process from COVID-19. We conducted in-depth individual interviews with participants enrolled in the Long-term Immunological Impact of Novel Coronavirus (LIINC) cohort study in San Francisco, California from June through October of 2020. Participants were adults who had a previously confirmed positive SARV-CoV-2 nucleic acid amplification test result, had recovered or were recovering from acute infection, and underwent serial evaluations at our clinical research center. We purposefully sampled 24 English- and Spanish-speaking adults with asymptomatic, mild and severe symptomatic infection, including those who were hospitalized, and those with HIV co-infection. Half of our sample (50.0%) identified as Latinx/Hispanic and most of the participants were men (62.5%). We used thematic analysis to characterize the illness experience, recovery process, and mental health impact of experiencing COVID-19 and present clinical data for each participant. Emergent themes were: (1) across symptom profiles and severity, experiencing COVID-19 was associated with psychological distress, (2) among participants with symptomatic infection, the illness experience was characterized by uncertainty in terms of managing symptoms and recovery, and (3) despite wide-ranging illness experiences, participants shared many common characteristics, including health information-seeking behavior facilitated by access to medical care, and uncertainty regarding the course of their illness and recovery. COVID-19 was associated with elevated levels of psychological distress, regardless of symptoms.

SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay

Serosurveillance studies are critical for estimating SARS-CoV-2 transmission and immunity, but interpretation of results is currently limited by poorly defined variability in the performance of antibody assays to detect seroreactivity over time in individuals with different clinical presentations. We measured longitudinal antibody responses to SARS-CoV-2 in plasma samples from a diverse cohort of 128 individuals over 160 days using 14 binding and neutralization assays. For all assays, we found a consistent and strong effect of disease severity on antibody magnitude, with fever, cough, hospitalization, and oxygen requirement explaining much of this variation. We found that binding assays measuring responses to spike protein had consistently higher correlation with neutralization than those measuring responses to nucleocapsid, regardless of assay format and sample timing. However, assays varied substantially with respect to sensitivity during early convalescence and in time to seroreversion. Variations in sensitivity and durability were particularly dramatic for individuals with mild infection, who had consistently lower antibody titers and represent the majority of the infected population, with sensitivities often differing substantially from reported test characteristics (e.g., amongst commercial assays, sensitivity at 6 months ranged from 33% for ARCHITECT IgG to 98% for VITROS Total Ig). Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on the severity of the initial infection, timing relative to infection, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

Long-Term SARS-CoV-2-Specific Immune and Inflammatory Responses Across a Clinically Diverse Cohort of Individuals Recovering from COVID-19

A detailed understanding of long-term SARS-CoV-2-specific T cell responses and their relationship to humoral immunity and markers of inflammation in diverse groups of individuals representing the spectrum of COVID-19 illness and recovery is urgently needed. Data are also lacking as to whether and how adaptive immune and inflammatory responses differ in individuals that experience persistent symptomatic sequelae months following acute infection compared to those with complete, rapid recovery. We measured SARS-CoV-2-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally up to 9 months following infection in a diverse group of 70 individuals with PCR-confirmed SARS-CoV-2 infection. The participants had varying degrees of initial disease severity and were enrolled in the northern California Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort. Adaptive T cell responses remained remarkably stable in all participants across disease severity during the entire study interval. Whereas the magnitude of the early CD4+ T cell immune response is determined by the severity of initial infection (participants requiring hospitalization or intensive care), pre-existing lung disease was significantly associated with higher long-term SARS-CoV2-specific CD8+ T cell responses, independent of initial disease severity or age. Neutralizing antibody levels were strongly correlated with SARS-CoV-2-specific CD4+ T but not CD8+ T cell responses. Importantly, we did not identify substantial differences in long-term virus-specific T cell or antibody responses between participants with and without COVID-19-related symptoms that persist months after initial infection.

Decrease in Hospitalizations for COVID-19 after Mask Mandates in 1083 U.S. Counties

WithdrawalThe authors have withdrawn this manuscript because there are increased rates of SARS- CoV-2 cases in the areas that we originally analyzed in this study. New analyses in the context of the third surge in the United States are therefore needed and will be undertaken directly in conjunction with the creators of the publicly-available databases on cases, hospitalizations, testing rates. Etc. We will be performing this in conjunction with machine learning experts at UCSF. Therefore, the authors do not wish this work to be cited as reference for the project. We hope to have an updated analysis using data from the 2nd and now 3rd wave of SARS-CoV-2 in this country soon. If you have any questions, please contact the corresponding author.

Evaluation of a novel community-based COVID-19 'Test-to-Care model' for low-income populations

BackgroundAfter a COVID-19 diagnosis, vulnerable populations face considerable logistical and financial challenges to isolate and quarantine. We developed and evaluated a novel, community-based approach ( Test-to-Care Model) designed to address these barriers for socioeconomically vulnerable Latinx individuals with newly diagnosed COVID-19 and their households. MethodsThis three-week demonstration project was nested within an epidemiologic surveillance study in a primarily Latinx neighborhood in the Mission district of San Francisco, California. The Test-to-Care model was developed with input from community members and public health leaders. Key components included: (1) provision of COVID-19-related education and information about available community resources, (2) home deliveries of material goods to facilitate safe isolation and quarantine (groceries, personal protective equipment and cleaning supplies), and (3) longitudinal clinical and social support. Newly SARS-CoV-2 PCR-positive participants were eligible to participate. Components of the model were delivered by the Test-to-Care team which was comprised of healthcare providers and community health workers (CHWs) who provided longitudinal clinic- and community-based support for the duration of the isolation period to augment existing services from the Department of Public Health (DPH). We evaluated the Test-to-Care Model using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Framework and drew upon multiple data sources including: programmatic data, informal interviews with participants and providers/CHWs and structured surveys among providers/CHWs. ResultsOverall, 83 participants in the surveillance study were diagnosed with COVID-19, of whom 95% (79/83) were Latinx and 88% (65/74) had an annual household income <$50,000. Ninety-six percent (80/83) of participants were reached for results disclosure, needs assessment and DPH linkage for contact tracing. Among those who underwent an initial needs assessment, 45% (36/80) were uninsured and 55% (44/80) were not connected to primary care. Sixty-seven percent (56/83) of participants requested community-based CHW support to safely isolate at their current address and 65% (54/83) of all COVID-19 participants received ongoing community support via CHWs for the entire self-isolation period. Participants reported that the intervention was highly acceptable and that their trust increased over time - this resulted in 9 individuals who disclosed a larger number of household members than first reported, and 6 persons who requested temporary relocation to a hotel room for isolation despite initially declining this service; no unintended harms were identified. The Test-to-Care Model was found to be both acceptable and feasible to providers and CHWs. Challenges identified included a low proportion of participants linked to primary care despite support (approximately 10% after one month), and insufficient access to financial support for wage replacement. ConclusionsThe Test-to-Care Model is a feasible and acceptable intervention for supporting self-isolation and quarantine among newly diagnosed COVID-19 patients and their households by directly addressing key barriers faced by vulnerable populations.

SARS-CoV-2 Community Transmission During Shelter-in-Place in San Francisco

BackgroundWe characterized SARS-CoV-2 infections in a densely-populated, majority Latinx San Francisco community six-weeks into the citys shelter-in-place order. MethodsWe offered SARS-CoV-2 reverse transcription-PCR and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (>4 years) and workers in a San Francisco census tract (population: 5,174) at outdoor, community-mobilized events over four days. We estimated SARS-CoV-2 point prevalence (PCR-positive) and cumulative incidence (antibody or PCR-positive) in the census tract and evaluated risk factors for recent (PCR-positive/antibody-negative) versus prior infection (antibody-positive/PCR-negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions. ResultsWe tested 3,953 persons: 40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black. Overall, 2.1% (83/3,871) tested PCR-positive: 95% were Latinx and 52% asymptomatic when tested. 1.7% of residents and 6.0% of workers (non-census tract residents) were PCR-positive. Among 2,598 census tract residents, estimated point prevalence of PCR-positives was 2.3% (95%CI: 1.2-3.8%): 3.9% (95%CI: 2.0-6.4%) among Latinx vs. 0.2% (95%CI: 0.0-0.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95%CI: 4.0-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter-in-place and maintain income, frontline service work, unemployment, and household income <$50,000/year. Five SARS-CoV-2 phylogenetic lineages were detected. ConclusionSARS-CoV-2 infections from diverse lineages continued circulating among low-income, Latinx persons unable to work from home and maintain income during San Franciscos shelter-in-place ordinance.