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1.
Open forum infectious diseases ; 2021.
Article in English | EuropePMC | ID: covidwho-1624185

ABSTRACT

BACKGROUND There is mounting evidence for the presence of post-acute sequelae of SARS-CoV-2 infection (PASC), but there is limited information on the spectrum, magnitude, duration, and patterns of these sequelae as well as their influence on quality of life. METHODS We assembled a cohort of adults with documented history of SARS-CoV-2 RNA-positivity who were ≥ 2 weeks past onset of COVID-19 symptoms or, if asymptomatic, first positive test. At 4-month intervals, we queried physical and mental health symptoms and quality of life. RESULTS Of the first 179 participants enrolled, 10 were asymptomatic during the acute phase of SARS-CoV-2 infection, 125 symptomatic but not hospitalized, and 44 symptomatic and hospitalized. During the post-acute phase, fatigue, shortness of breath, concentration problems, headaches, trouble sleeping and anosmia/dysgeusia were most common through 8 months of observation. Symptoms were typically at least somewhat bothersome and sometimes exhibited a waxing-and-waning course. Some participants experienced symptoms of depression, anxiety, and post-traumatic stress, as well as difficulties with performance of usual activities. The median visual analogue scale rating of general health was lower at 4 and 8 months compared to pre-COVID-19. Two clusters of symptom domains were identified. CONCLUSION Many participants report bothersome symptoms following onset of COVID-19 with variable patterns of persistence and impact on quality of life. The substantial variability suggests the existence of multiple sub-phenotypes of PASC. A rigorous approach to the prospective measurement of symptoms and functional manifestations sets the stage for the next phase of research focusing on the pathophysiologic causes of the various sub-groups of PASC.

2.
Ann Clin Transl Neurol ; 2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1624961

ABSTRACT

Cognitive post-acute sequelae of SARS-CoV-2 (PASC) can occur after mild COVID-19. Detailed clinical characterizations may inform pathogenesis. We evaluated 22 adults reporting cognitive PASC and 10 not reporting cognitive symptoms after mild SARS-CoV-2 infection through structured interviews, neuropsychological testing, and optional cerebrospinal fluid (CSF) evaluations (53%). Delayed onset of cognitive PASC occurred in 43% and associated with younger age. Cognitive PASC participants had a higher number of pre-existing cognitive risk factors (2.5 vs. 0; p = 0.03) and higher proportion with abnormal CSF findings (77% vs. 0%; p = 0.01) versus controls. Cognitive risk factors and immunologic mechanisms may contribute to cognitive PASC pathogenesis.

3.
Int J Behav Med ; 2021 Dec 16.
Article in English | MEDLINE | ID: covidwho-1588715

ABSTRACT

BACKGROUND: There is an urgent need to fully understand the impact of variable COVID-19 experiences and the optimal management of post-acute sequelae of SARS-CoV-2 infection. We characterized the variability in the acute illness experience and ongoing recovery process from participants in a COVID-19 recovery cohort study in Northern California in 2020. METHOD: We completed 24 semi-structured in-depth interviews with adults with confirmed positive SARV-CoV-2 nucleic acid amplification test result, had recovered or were recovering from acute infection, and underwent serial evaluations. We purposefully sampled English- and Spanish-speaking adults with asymptomatic, mild, and severe symptomatic infection, including those who were hospitalized and those with HIV co-infection. We used a thematic analysis to analyze interviews and identify salient themes. RESULTS: After integrating the thematic analysis with clinical data, we identified key themes: (1) across symptom profiles and severity, experiencing COVID-19 was associated with psychological distress; (2) symptomatic infection carried uncertainty in symptom presentation and ongoing recovery (e.g., long COVID); and (3) health information-seeking behavior was facilitated by access to medical care and uncertainty with the recovery process. CONCLUSION: Our data informs the emerging field of "long COVID" research and shows a need to provide information and continuous support to persons with post-acute sequelae to ensure they feel secure along the path to recovery.

4.
BMJ Glob Health ; 6(11)2021 11.
Article in English | MEDLINE | ID: covidwho-1515293

ABSTRACT

INTRODUCTION: As of 26 March 2021, the Africa Centres for Disease Control and Prevention had reported 4 159 055 cases of COVID-19 and 111 357 deaths among the 55 African Union member states; however, no country has published a nationally representative serosurvey as of October 2021. Such data are vital for understanding the pandemic's progression on the continent, evaluating containment measures, and policy planning. METHODS: We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was estimated after applying sampling weights. RESULTS: The overall weighted seroprevalence was 2.6% (95% CI 1.9% to 3.4%). This was 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0% to 2.5%), and urban seropositivity was 4.2% (95% CI 2.6% to 5.7%). DISCUSSION: Overall seroprevalence was low compared with countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone). This has ramifications for the country's third wave (which started in June 2021), during which the average number of daily reported cases was 87 by the end of the month:this could potentially be on the order of 3700 actual infections per day, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant under-reporting of incidence and mortality across the continent.


Subject(s)
COVID-19 , SARS-CoV-2 , Cross-Sectional Studies , Humans , Prevalence , Seroepidemiologic Studies , Sierra Leone/epidemiology
5.
Am J Trop Med Hyg ; 2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1371037

ABSTRACT

As the fight against the coronavirus disease 2019 (COVID-19) pandemic continues, the necessity for wide-scale, global vaccine rollout to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and slow its mutation rate remains unassailable. The COVID-19 Vaccines Global Access (COVAX) initiative's campaign involves a proportional framework to finance and distribute SARS-CoV-2 vaccines in low- and middle-income countries. However, the COVAX framework has critical limitations, including limited funding and the failure to account for the special epidemic risks and needs of its participating nations, as recommended by the World Health Organization's Strategic Advisory Group of Experts on Immunization framework. These drawbacks disproportionately impact Africa, where many nations rely on COVAX as their main source of vaccines. The current plan to vaccinate only up to 20% of participating nations' populations is short-sighted from both epidemiologic and moral perspectives. COVAX must commit to vaccinating all of Africa and its initiative must be modified to account for the health and economic infrastructures in these countries. Lessons learned from successful vaccination campaigns, including the West African Ebola outbreak, have shown that vaccinating all of Africa is possible and feasible, and that infrastructure and human resources can support mass vaccination. To halt this global pandemic, global responsibility must be accepted to finance and equitably distribute SARS-CoV-2 vaccines to African nations. We urge COVAX to act swiftly to prevent Africa from becoming the new face of a persisting pandemic.

6.
Cell Rep ; 36(6): 109518, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1345269

ABSTRACT

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR-confirmed SARS-CoV-2 infection. Participants represent a spectrum of illness and recovery, including some with persistent viral shedding in saliva and many experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). T cell responses remain stable for up to 9 months. Whereas the magnitude of early CD4+ T cell immune responses correlates with severity of initial infection, pre-existing lung disease is independently associated with higher long-term SARS-CoV-2-specific CD8+ T cell responses. Among participants with PASC 4 months following coronavirus disease 2019 (COVID-19) symptom onset, we observe a lower frequency of CD8+ T cells expressing CD107a, a marker of degranulation, in response to Nucleocapsid (N) peptide pool stimulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8+ T cells. Neutralizing antibody levels strongly correlate with SARS-CoV-2-specific CD4+ T cell responses.


Subject(s)
COVID-19/complications , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/pathology , Disease Progression , Female , Humans , Male , Middle Aged , Severity of Illness Index , Virus Shedding/immunology
7.
Sci Adv ; 7(31)2021 Jul.
Article in English | MEDLINE | ID: covidwho-1334521

ABSTRACT

Interpretation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveillance studies is limited by poorly defined performance of antibody assays over time in individuals with different clinical presentations. We measured antibody responses in plasma samples from 128 individuals over 160 days using 14 assays. We found a consistent and strong effect of disease severity on antibody magnitude, driven by fever, cough, hospitalization, and oxygen requirement. Responses to spike protein versus nucleocapsid had consistently higher correlation with neutralization. Assays varied substantially in sensitivity during early convalescence and time to seroreversion. Variability was dramatic for individuals with mild infection, who had consistently lower antibody titers, with sensitivities at 6 months ranging from 33 to 98% for commercial assays. Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on infection severity, timing, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.

8.
JAMA Netw Open ; 4(6): e2113031, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1261749

ABSTRACT

Importance: The US Department of Veterans Affairs (VA) offers programs that reduce barriers to care for veterans and those with housing instability, poverty, and substance use disorder. In this setting, however, the role that social and behavioral risk factors play in COVID-19 outcomes is unclear. Objective: To examine whether social and behavioral risk factors were associated with mortality among US veterans with COVID-19 and whether this association might be modified by race/ethnicity. Design, Setting, and Participants: This cohort study obtained data from the VA Corporate Data Warehouse to form a cohort of veterans who received a positive COVID-19 test result between March 2 and September 30, 2020, in a VA health care facility. All veterans who met the inclusion criteria were eligible to participate in the study, and participants were followed up for 30 days after the first SARS-CoV-2 or COVID-19 diagnosis. The final follow-up date was October 31, 2020. Exposures: Social risk factors included housing problems and financial hardship. Behavioral risk factors included current tobacco use, alcohol use, and substance use. Main Outcomes and Measures: The primary outcome was all-cause mortality in the 30-day period after the SARS-CoV-2 or COVID-19 diagnosis date. Multivariable logistic regression was used to estimate odds ratios, clustering for health care facilities and adjusting for age, sex, race, ethnicity, marital status, clinical factors, and month of COVID-19 diagnosis. Results: Among 27 640 veterans with COVID-19 who were included in the analysis, 24 496 were men (88.6%) and the mean (SD) age was 57.2 (16.6) years. A total of 3090 veterans (11.2%) had housing problems, 4450 (16.1%) had financial hardship, 5358 (19.4%) used alcohol, and 3569 (12.9%) reported substance use. Hospitalization occurred in 7663 veterans (27.7%), and 1230 veterans (4.5%) died. Housing problems (adjusted odds ratio [AOR], 0.96; 95% CI, 0.77-1.19; P = .70), financial hardship (AOR, 1.13; 95% CI, 0.97-1.31; P = .11), alcohol use (AOR, 0.82; 95% CI, 0.68-1.01; P = .06), current tobacco use (AOR, 0.85; 95% CI, 0.68-1.06; P = .14), and substance use (AOR, 0.90; 95% CI, 0.71-1.15; P = .41) were not associated with higher mortality. Interaction analyses by race/ethnicity did not find associations between mortality and social and behavioral risk factors. Conclusions and Relevance: Results of this study showed that, in an integrated health system such as the VA, social and behavioral risk factors were not associated with mortality from COVID-19. Further research is needed to substantiate the potential of an integrated health system to be a model of support services for households with COVID-19 and populations who are at risk for the disease.


Subject(s)
COVID-19/mortality , Housing , Pandemics , Poverty , Substance-Related Disorders , Veterans , Adult , Aged , Alcohol Drinking , COVID-19/ethnology , Cohort Studies , Female , Homeless Persons , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Risk Factors , SARS-CoV-2 , Tobacco Use , United States/epidemiology , United States Department of Veterans Affairs
10.
Biomark Res ; 9(1): 29, 2021 May 01.
Article in English | MEDLINE | ID: covidwho-1209031

ABSTRACT

BACKGROUND: Hospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients. METHODS: We retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts. RESULTS: The analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345-0.657, p < 0.001) with longer median survival (14 days vs 8 days, p < 0.001), but these associations were not observed in the overall cohort (p = 0.063). Additionally, no significant difference in mortality was found between patients receiving empiric therapeutic AC versus prophylactic AC in various subgroups with different D-dimer level cutoffs. Patients who received therapeutic AC showed a higher incidence of major bleeding (13.8% vs 3.9%, p < 0.001). Furthermore, patients with a HAS-BLED score of ≥2 had a higher risk of mortality (HR 1.482, 95% CI 1.110-1.980, p = 0.008), while those with a score of ≥3 had a higher risk of major bleeding (Odds ratio: 1.883, CI: 1.114-3.729, p = 0.016). CONCLUSION: Empiric use of therapeutic AC conferred survival benefit to patients requiring invasive mechanical ventilation, but did not show benefit in non-critically ill patients hospitalized for COVID-19. Careful bleeding risk estimation should be pursued before considering escalation of AC intensity.

11.
J Neurovirol ; 27(1): 191-195, 2021 02.
Article in English | MEDLINE | ID: covidwho-1059483

ABSTRACT

As cases of coronavirus disease 2019 (COVID-19) mount worldwide, attention is needed on potential long-term neurologic impacts for the majority of patients who experience mild to moderate illness managed as outpatients. To date, there has not been discussion of persistent neurocognitive deficits in patients with milder COVID-19. We present two cases of non-hospitalized patients recovering from COVID-19 with persistent neurocognitive symptoms. Commonly used cognitive screens were normal, while more detailed testing revealed working memory and executive functioning deficits. An observational cohort study of individuals recovering from COVID-19 (14 or more days following symptom onset) identified that among the first 100 individuals enrolled, 14 were non-hospitalized patients reporting persistent cognitive issues. These 14 participants had a median age of 39 years (interquartile range: 35-56), and cognitive symptoms were present for at least a median of 98 days (interquartile range: 71-120 following acute COVID-19 symptoms); no participants with follow-up evaluation reported symptom resolution. We discuss potential mechanisms to be explored in future studies, including direct viral effects, indirect consequences of immune activation, and immune dysregulation causing auto-antibody production.


Subject(s)
COVID-19/physiopathology , Cognitive Dysfunction/physiopathology , SARS-CoV-2/pathogenicity , Adult , COVID-19/complications , COVID-19/immunology , COVID-19/virology , Cognitive Dysfunction/complications , Cognitive Dysfunction/immunology , Cognitive Dysfunction/virology , Executive Function/physiology , Female , Humans , Memory, Short-Term/physiology , Middle Aged , Neuropsychological Tests , Outpatients , Time Factors
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