Long COVID outcomes following omicron wave in non-hospital population.

Background: The persistence of symptoms or the development of new symptoms following a diagnosis of SARS-CoV-2 has given rise to a multifaceted clinical condition referred to as "long COVID" (LC). The understanding of LC among China's non-hospitalized population continues to be insufficient. This investigation was designed to evaluate the protracted consequences amongst this demographic, as well as to identify the associated risk factors. Methods: This research constitutes a prospective cohort study focusing on non-hospitalized individuals, aged between 18 and 59, who have been positively diagnosed with COVID-19. Each participant was subjected to a sequence of questionnaire-based surveys, designed to evaluate symptoms as well as the status of depression and anxiety. A logistic regression model, adjusted for multiple variables, was employed to scrutinize the correlation between demographic elements, lifestyle attributes, and health-related risk factors in relation to conditions and symptoms post COVID-19 infection. Results: A total of 706 individuals participated in the 3 months follow-up, with 620 continuing on to the 6 months follow-up. The median age was 35 (28, 43) years, and 597 (85%) are female. Upon follow-up, Compared with patients without LC, patients with LC have a higher proportion of females (420 (87%) vs. 177 (79%); p = 0.010), were older (35 (29, 44) years vs. 33 (27, 41) years; p = 0.010) and have more comorbidities. Out of all participants, 483 (68.4%) reported experiencing at least one symptom at the 3 months mark, while 49.7% reported symptoms persisting at the 6 months mark. At the 3 months follow-up, the most prevalent persistent symptoms were cough (46%), fatigue (38%), and shortness of breath (34%). By the 6 months follow-up, fatigue (25%), shortness of breath (22%), and sleep disorders (16%) were the most commonly reported symptoms. Anxiety and depression were consistently reported as prevalent symptoms throughout the follow-up period. Most patient symptoms fade over time, with the quickest decreases observed in cough (from 46 to 9%), expectoration (from 26 to 6.3%), smell disorder (from 16 to 3.9%), and taste disorder (from 18 to 3.5%). Male and those possessing advanced educational qualifications exhibit a decreased susceptibility to the sustained incidence of coughing. Conversely, older age and the presence of comorbidities were identified as risk factors for persistent fatigue and shortness of breath. Conclusion: In the after of COVID-19, it has been observed that the majority of patient symptoms tend to decrease over time. The primary residual symptoms noticed after a 6 month follow-up were fatigue, dyspnea, and sleep disturbances. However, it's noteworthy that the risk factors associated with these symptoms exhibit subtle variations. Furthermore, psychological sequelae, namely depression and anxiety, are frequently reported among COVID-19 survivors.

Changes in prevalence of anxiety and depression among COVID-19 patients during a two-year recovery period: A systematic review and meta-analysis.

OBJECTIVE: To analyze the temporal trend of anxiety and depression prevalences up to 2 years of follow-up for COVID-19 patients during the recovery period and to compare regional differences. METHODS: We performed a systematic review from PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP using keywords such as "COVID-19", "anxiety", "depression", and "cohort study". Meta-analysis was performed to estimate the pooled prevalence of anxiety and depression at five follow-up time intervals. Subgroup analyses were conducted by different regions. RESULTS: 34 cohort studies were included in the meta-analyses. The pooled anxiety prevalence rates at 0-1 month, 1-3 months, 3-6 months, 6-12 months and 12-24 months were 18% (95% CI: 11% to 28%), 18% (95% CI: 12% to 28%), 22% (95% CI: 16% to 29%), 15% (95% CI: 11% to 21%), and 10% (95% CI: 0.05% to 20%), respectively, and the pooled depression prevalence rates were 22% (95%CI: 15% to 33%), 19% (95% CI: 13% to 29%), 21% (95% CI: 15% to 28%), 15% (95% CI: 11% to 20%), and 9% (95% CI: 0.4% to 21%) respectively. The prevalence of depression in Asian and non-Asian countries was statistically different at 0-1 month (χ2 = 15.248, P < 0.001) and 1-3 months (χ2 = 28.298, P < 0.001), and prevalence of anxiety was statistically different at 3-6 months (χ2 = 9.986, P = 0.002) and 6-12 months (χ2 = 7.378, P = 0.007). CONCLUSION: The prevalence of anxiety and depression in COVID-19 patients generally tends to decrease after 2 years of recovery, but may temporarily increase at 3-6 months. There are regional differences in the changes in prevalence of anxiety and depression.

Decline in case rates of youth onset type 2 diabetes in year three of the COVID-19 pandemic.

OBJECTIVES: To determine changes in case rates of youth onset type 2 diabetes in the three years following the COVID-19 pandemic. METHODS: A single-center, retrospective medical record review was conducted for patients newly diagnosed with T2D between 3/1/18 and 2/28/23 at a pediatric tertiary care center. The number of patients referred to CHLA with a T2D diagnosis date between 3/1/2020 and 2/28/2023 was compared to historical rates between 3/1/2018 and 2/29/2020. χ2 or Fisher's exact test was used to compare categorical variables between each year and 2019. RESULTS: Compared to prepandemic baseline (3/1/19-2/29/20, 11.8±3.7 cases/month), there was a significant increase in new T2D monthly case rates in pandemic year 1 (3/1/20-2/28/21, 20.1±6.0 cases/month, 171 %, p=0.005) and pandemic year 2 (3/1/21-2/28/22, 25.9±8.9 cases/month, 221 %, p=0.002). Case rates declined in pandemic year 3 to 14.5±4.1 cases/month (3/1/22-2/28/23, p=0.43). Compared to prepandemic year 1, the frequency of DKA at diagnosis was higher in pandemic year 1 (13.3 vs. 5.0 %, p=0.009). The DKA rate in pandemic years 2 (6.8 %) and 3 (3.4 %) were comparable to prepandemic year 1 (p=0.53 and 0.58, respectively). CONCLUSIONS: Youth onset type 2 diabetes cases and DKA rates in year 3 of the pandemic have returned to prepandemic level.

Prevalence and drivers of nurse and physician distress in cardiovascular and oncology programmes at a Canadian quaternary hospital network during the COVID-19 pandemic: a quality improvement initiative.

OBJECTIVES: To assess the prevalence and drivers of distress, a composite of burnout, decreased meaning in work, severe fatigue, poor work-life integration and quality of life, and suicidal ideation, among nurses and physicians during the COVID-19 pandemic. DESIGN: Cross-sectional design to evaluate distress levels of nurses and physicians during the COVID-19 pandemic between June and August 2021. SETTING: Cardiovascular and oncology care settings at a Canadian quaternary hospital network. PARTICIPANTS: 261 nurses and 167 physicians working in cardiovascular or oncology care. Response rate was 29% (428 of 1480). OUTCOME MEASURES: Survey tool to measure clinician distress using the Well-Being Index (WBI) and additional questions about workplace-related and COVID-19 pandemic-related factors. RESULTS: Among 428 respondents, nurses (82%, 214 of 261) and physicians (62%, 104 of 167) reported high distress on the WBI survey. Higher WBI scores (≥2) in nurses were associated with perceived inadequate staffing (174 (86%) vs 28 (64%), p=0.003), unfair treatment, (105 (52%) vs 11 (25%), p=0.005), and pandemic-related impact at work (162 (80%) vs 22 (50%), p<0.001) and in their personal life (135 (67%) vs 11 (25%), p<0.001), interfering with job performance. Higher WBI scores (≥3) in physicians were associated with perceived inadequate staffing (81 (79%) vs 32 (52%), p=0.001), unfair treatment (44 (43%) vs 13 (21%), p=0.02), professional dissatisfaction (29 (28%) vs 5 (8%), p=0.008), and pandemic-related impact at work (84 (82%) vs 35 (56%), p=0.001) and in their personal life (56 (54%) vs 24 (39%), p=0.014), interfering with job performance. CONCLUSION: High distress was common among nurses and physicians working in cardiovascular and oncology care settings during the pandemic and linked to factors within and beyond the workplace. These results underscore the complex and contextual aspects of clinician distress, and the need to develop targeted approaches to effectively address this problem.

Trends in COVID-19 admissions and deaths among people living with HIV in South Africa: analysis of national surveillance data.

BACKGROUND: In 2021, the HIV prevalence among South African adults was 18% and more than 2 million people had uncontrolled HIV and, therefore, had increased risk of poor outcomes with SARS-CoV-2 infection. We investigated trends in COVID-19 admissions and factors associated with in-hospital COVID-19 mortality among people living with HIV and people without HIV. METHODS: In this analysis of national surveillance data, we linked and analysed data collected between March 5, 2020, and May 28, 2022, from the DATCOV South African national COVID-19 hospital surveillance system, the SARS-CoV-2 case line list, and the Electronic Vaccination Data System. All analyses included patients hospitalised with SARS-CoV-2 with known in-hospital outcomes (ie, who were discharged alive or had died) at the time of data extraction. We used descriptive statistics for admissions and mortality trends. Using post-imputation random-effect multivariable logistic regression models, we compared characteristics and the case fatality ratio of people with HIV and people without HIV. Using modified Poisson regression models, we compared factors associated with mortality among all people with COVID-19 admitted to hospital and factors associated with mortality among people with HIV. FINDINGS: Among 397 082 people with COVID-19 admitted to hospital, 301 407 (75·9%) were discharged alive, 89 565 (22·6%) died, and 6110 (1·5%) had no recorded outcome. 270 737 (68·2%) people with COVID-19 had documented HIV status (22 858 with HIV and 247 879 without). Comparing characteristics of people without HIV and people with HIV in each COVID-19 wave, people with HIV had increased odds of mortality in the D614G (adjusted odds ratio 1·19, 95% CI 1·09-1·29), beta (1·08, 1·01-1·16), delta (1·10, 1·03-1·18), omicron BA.1 and BA.2 (1·71, 1·54-1·90), and omicron BA.4 and BA.5 (1·81, 1·41-2·33) waves. Among all COVID-19 admissions, mortality was lower among people with previous SARS-CoV-2 infection (adjusted incident rate ratio 0·32, 95% CI 0·29-0·34) and with partial (0·93, 0·90-0·96), full (0·70, 0·67-0·73), or boosted (0·50, 0·41-0·62) COVID-19 vaccination. Compared with people without HIV who were unvaccinated, people without HIV who were vaccinated had lower risk of mortality (0·68, 0·65-0·71) but people with HIV who were vaccinated did not have any difference in mortality risk (1·08, 0·96-1·23). In-hospital mortality was higher for people with HIV with CD4 counts less than 200 cells per µL, irrespective of viral load and vaccination status. INTERPRETATION: HIV and immunosuppression might be important risk factors for mortality as COVID-19 becomes endemic. FUNDING: South African National Institute for Communicable Diseases, the South African National Government, and the United States Agency for International Development.

Clinical outcomes in hospitalized plasma and platelet transfusion recipients prior to and following widespread blood donor SARS-CoV-2 infection and vaccination.

BACKGROUND: The safety of transfusion of SARS-CoV-2 antibodies in high plasma volume blood components to recipients without COVID-19 is not established. We assessed whether transfusion of plasma or platelet products during periods of increasing prevalence of blood donor SARS-CoV-2 infection and vaccination was associated with changes in outcomes in hospitalized patients without COVID-19. METHODS: We conducted a retrospective cohort study of hospitalized adults who received plasma or platelet transfusions at 21 hospitals during pre-COVID-19 (3/1/2018-2/29/2020), COVID-19 pre-vaccine (3/1/2020-2/28/2021), and COVID-19 post-vaccine (3/1/2021-8/31/2022) study periods. We used multivariable logistic regression with generalized estimating equations to adjust for demographics and comorbidities to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 21,750 hospitalizations of 18,584 transfusion recipients without COVID-19, there were 697 post-transfusion thrombotic events, and oxygen requirements were increased in 1751 hospitalizations. Intensive care unit length of stay (n = 11,683) was 3 days (interquartile range 1-5), hospital mortality occurred in 3223 (14.8%), and 30-day rehospitalization in 4144 (23.7%). Comparing the pre-COVID, pre-vaccine and post-vaccine study periods, there were no trends in thromboses (OR 0.9 [95% CI 0.8, 1.1]; p = .22) or oxygen requirements (OR 1.0 [95% CI 0.9, 1.1]; p = .41). In parallel, there were no trends across study periods for ICU length of stay (p = .83), adjusted hospital mortality (OR 1.0 [95% CI 0.9-1.0]; p = .36), or 30-day rehospitalization (p = .29). DISCUSSION: Transfusion of plasma and platelet blood components collected during the pre-vaccine and post-vaccine periods of the COVID-19 pandemic was not associated with increased adverse outcomes in transfusion recipients without COVID-19.

Bacterial nasopharyngeal colonisation in children in South Africa before and during the COVID-19 pandemic: an observational study.

BACKGROUND: Deployment of non-pharmaceutical interventions such as face masking and physical distancing during the COVID-19 pandemic could have altered the transmission dynamics and carriage of respiratory organisms. We evaluated colonisation with Streptococcus pneumoniae and other upper respiratory tract bacterial colonisers before and during the COVID-19 pandemic. METHODS: We did two cross-sectional surveys in Soweto, South Africa from July 3 to Dec 13, 2018 (pre-COVID-19 period) and from Aug 4, 2021, to March 31, 2022 (COVID-19 period) in healthy children (aged ≤60 months) who had recorded HIV status and had not received antibiotics in the 21 days before enrolment. At enrolment, we collected nasopharyngeal swab samples from child participants. Following nucleic acid extraction, nanofluidic quantitative PCR was used to screen all samples for 92 S pneumoniae serotypes and 14 other bacteria. The primary objective was to compare the prevalence and density of pneumococcal nasopharyngeal colonisation, overall and stratified by 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and non-vaccine serotypes. Secondary study objectives included a comparison of serotype-specific pneumococcal colonisation and density, as well as colonisation by the 14 other bacteria in the COVID-19 versus pre-COVID-19 period. We used an adjusted multiple logistic and linear regression model to compare the colonisation prevalence and density between study periods. FINDINGS: We analysed nasopharyngeal swabs from 1107 children (n=571 in the pre-COVID-19 period; n=536 in the COVID-19 period). We observed no change in overall pneumococcal colonisation between periods (274 [51%] of 536 in the COVID-19 period vs 282 [49%] of 571 in the pre-COVID-19 period; adjusted odds ratio [aOR] 1·03 [95% CI 0·95-1·12]). The prevalence of PCV13 serotypes was lower in the COVID-19 than in the pre-COVID-19 period (72 [13%] vs 106 [19%]; 0·87 [0·78-0·97]), whereas the prevalence of non-typeable S pneumoniae was higher (34 [6%] vs 63 [12%]; 1·30 [1·12-1·50]). The mean log10 density for overall pneumococcal colonisation was lower in the COVID-19 period than in the pre-COVID-19 period (3·96 [95% CI 3·85-4·07] vs 4·72 [4·63-4·80] log10 genome equivalents per mL; p<0·0001). A lower density of non-vaccine serotypes (3·63 [3·51-3·74] vs 4·08 [3·95-4·22] log10 genome equivalents per mL; p<0·0001) and non-typeable S pneumoniae (3·11 [2·94-3·29] vs 4·41 [4·06-4·75] log10 genome equivalents per mL; p<0·00001) was also observed in the COVID-19 period. There was no difference in the density of PCV13 serotypes between the periods. The prevalence of colonisation during the COVID-19 versus pre-COVID-19 period was lower for non-typeable Haemophilus influenzae (280 [49%] vs 165 [31%]; aOR 0·77 [95% CI 0·71-0·84]), Moraxella catarrhalis (328 [57%] vs 242 [45%]; 0·85 [0·79-0·92]), and Neisseria lactamica (51 [9%] vs 13 [2%]; 0·64 [0·52-0·78]), but higher for Acinetobacter baumannii (34 [6%] vs 102 [19%]; 1·55 [1·35-1·77]) and Staphylococcus aureus (29 [5%] vs 52 [10%]; 1·28 [1·10-1·50]). INTERPRETATION: There were variable effects on the colonisation prevalence and density of bacterial organisms during the COVID-19 compared with the pre-COVID-19 period. The lower prevalence of PCV13 serotype together with other respiratory organisms including non-typeable H influenzae and M catarrhalis could have in part contributed to a decrease in all-cause lower respiratory tract infections observed in South Africa during the initial stage of the COVID-19 pandemic. The pathophysiological mechanism for the increase in A baumannii and S aureus colonisation warrants further investigation, as does the clinical relevance of these findings. FUNDING: The Bill & Melinda Gates Foundation.

[Assessment of occupational hazards and their prevention in the work of dental technicians during the COVID-19 pandemic]. / Ocena zagrozen zawodowych oraz ich profilaktyka w pracy techników dentystycznych w czasie pandemii COVID-19.

BACKGROUND: Work of a dental technician is associated with exposure to a number of harmful factors. We can distinguish: chemical, biological, physical and psychophysical factors. They contribute to many diseases, but not all of them are classified as occupational diseases. The main aim of the study was to assess the health hazards that occur in the workplace of a dental technician and their prevention during the COVID-19 pandemic. MATERIAL AND METHODS: An epidemiological cross-sectional study was conducted. A self-created questionnaire form containing 28 questions was used. The link to the survey was shared on social groups associating dental technicians. Participation in the study did not require logging in. During the data collection, the respondents' personal data were not collected and processed. RESULTS: 148 dental technicians participated in the study. The largest group were participants aged 21-25 (32%), the smallest group were people over 50 (6%). The most frequently occupied position was acrylic and plaster. More than 1/3 of those surveyed reported having allergies, most often to acrylic or metal. More than 20% of technicians reported experience of mechanical injuries several times a week or more. 17% of technicians declared professional burnout. 80% of technicians used protective clothing. Personal protective equipment was always used by only 22% of technicians, and as many as 29% of respondents never used the listed protective equipment. CONCLUSIONS: Not all dental laboratories were equipped with the necessary personal protective equipment. The most commonly used personal protective equipment included: disposable gloves, disinfectant liquid and extract. The COVID-19 pandemic contributed to a change in disinfection procedures in more than 1/3 of the respondents. 35% of them started using disinfection only after the outbreak of the pandemic, while most of the changes concerned the improvement of existing procedures. The length of work experience of technicians had an impact on exposure to stress and occupational burnout. Med Pr Work Health Saf. 2023;74(4):289-99.

Coverage with Selected Vaccines and Exemption from School Vaccine Requirements Among Children in Kindergarten - United States, 2022-23 School Year.

U.S. states and local jurisdictions set vaccination requirements for school attendance and conditions and procedures for exemptions from these requirements. States annually report data to CDC on the number of children in kindergarten who meet, are exempt from, or are in the process of meeting requirements. National- and state-level estimates for complete vaccination with measles, mumps, and rubella vaccine (MMR); diphtheria, tetanus, and acellular pertussis vaccine (DTaP); poliovirus vaccine (polio); and varicella vaccine (VAR); exemptions from vaccination; and legally allowed kindergarten attendance while meeting requirements were based on data reported by 49 states and the District of Columbia (DC) for the 2022-23 school year. This kindergarten class became age-eligible to complete most state-required vaccinations during the COVID-19 pandemic. National coverage remained near 93% for all vaccines; exemptions were low but increased to 3%, compared with those during the 2021-22 school year (2.6%). At the state level, coverage with MMR, DTaP, polio, and VAR decreased in 29, 31, 28, and 25 states, respectively, compared with coverage during the 2021-22 school year. Exemptions increased in 40 states and DC, with 10 states reporting an exemption from at least one vaccine for >5% of kindergartners. Schools and providers should work to ensure that students are vaccinated before school entry, such as during the enrollment process, which is often several months before school starts. State and local provisional enrollment periods that allow students to attend school while on a catch-up schedule also provide the opportunity to fully vaccinate students and to prevent nonmedical exemptions resulting from lingering undervaccination due to COVID-19 pandemic-related barriers to vaccination, such as reduced access to vaccination appointments.

Functional recovery in a cohort of ECMO and non-ECMO acute respiratory distress syndrome survivors.

BACKGROUND: The mortality benefit of VV-ECMO in ARDS has been extensively studied, but the impact on long-term functional outcomes of survivors is poorly defined. We aimed to assess the association between ECMO and functional outcomes in a contemporaneous cohort of survivors of ARDS. METHODS: Multicenter retrospective cohort study of ARDS survivors who presented to follow-up clinic. The primary outcome was FVC% predicted. Univariate and multivariate regression models were used to evaluate the impact of ECMO on the primary outcome. RESULTS: This study enrolled 110 survivors of ARDS, 34 of whom were managed using ECMO. The ECMO cohort was younger (35 [28, 50] vs. 51 [44, 61] years old, p < 0.01), less likely to have COVID-19 (58% vs. 96%, p < 0.01), more severely ill based on the Sequential Organ Failure Assessment (SOFA) score (7 [5, 9] vs. 4 [3, 6], p < 0.01), dynamic lung compliance (15 mL/cmH20 [11, 20] vs. 27 mL/cmH20 [23, 35], p < 0.01), oxygenation index (26 [22, 33] vs. 9 [6, 11], p < 0.01), and their need for rescue modes of ventilation. ECMO patients had significantly longer lengths of hospitalization (46 [27, 62] vs. 16 [12, 31] days, p < 0.01) ICU stay (29 [19, 43] vs. 10 [5, 17] days, p < 0.01), and duration of mechanical ventilation (24 [14, 42] vs. 10 [7, 17] days, p < 0.01). Functional outcomes were similar in ECMO and non-ECMO patients. ECMO did not predict changes in lung function when adjusting for age, SOFA, COVID-19 status, or length of hospitalization. CONCLUSIONS: There were no significant differences in the FVC% predicted, or other markers of pulmonary, neurocognitive, or psychiatric functional recovery outcomes, when comparing a contemporaneous clinic-based cohort of survivors of ARDS managed with ECMO to those without ECMO.

Effectiveness of BNT162b2 BA.4/5 bivalent mRNA vaccine against a range of COVID-19 outcomes in a large health system in the USA: a test-negative case-control study.

BACKGROUND: XBB-related omicron sublineages have recently replaced BA.4/5 as the predominant omicron sublineages in the USA and other regions globally. Despite preliminary signs of immune evasion of XBB sublineages, few data exist describing the real-world effectiveness of bivalent COVID-19 vaccines, especially against XBB-related illness. We aimed to investigate the effectiveness of the Pfizer--BioNTech BNT162b2 BA.4/5 bivalent vaccine against both BA.4/5-related and XBB-related disease in adults aged 18 years or older. METHODS: In this test-negative case-control study, we estimated the effectiveness of the BNT162b2 BA.4/5 bivalent vaccine using data from electronic health records of Kaiser Permanente Southern California health system members aged 18 years or older who received at least two doses of the wild-type COVID-19 mRNA vaccines. Participants sought care for acute respiratory infection between Aug 31, 2022, and April 15, 2023, and were tested for SARS-CoV-2 via PCR tests. Relative vaccine effectiveness (≥2 doses of wild-type mRNA vaccine plus a BNT162b2 BA.4/5 bivalent booster vs ≥2 doses of a wild-type mRNA vaccine alone) and absolute vaccine effectiveness (vs unvaccinated individuals) was estimated against critical illness related to acute respiratory infection (intensive care unit [ICU] admission, mechanical ventilation, or inpatient death), hospital admission, emergency department or urgent care visits, and in-person outpatient encounters with odds ratios from logistic regression models adjusted for demographic and clinical factors. We stratified vaccine effectiveness estimates for hospital admission, emergency department or urgent care visits, and outpatient encounters by omicron sublineage (ie, likely BA.4/5-related vs likely XBB-related), time since bivalent booster receipt, age group, number of wild-type doses received, and immunocompromised status. This study is registered with ClinicalTrials.gov (NCT04848584). FINDINGS: Analyses were conducted for 123 419 encounters (24 246 COVID-19 cases and 99 173 test-negative controls), including 4131 episode of critical illness (a subset of hospital admissions), 14 529 hospital admissions, 63 566 emergency department or urgent care visits, and 45 324 outpatient visits. 20 555 infections were BA.4/5 related and 3691 were XBB related. In adjusted analyses, relative vaccine effectiveness for those who received the BNT162b2 BA.4/5 bivalent booster compared with those who received at least two doses of a wild-type mRNA vaccine alone was an additional 50% (95% CI 23-68) against critical illness, an additional 39% (28-49) against hospital admission, an additional 35% (30-40) against emergency department or urgent care visits, and an additional 28% (22-33) against outpatient encounters. Waning of the bivalent booster from 0-3 months to 4-7 months after vaccination was evident for outpatient outcomes but was not detected for critical illness, hospital admission, and emergency department or urgent care outcomes. The relative effectiveness of the BNT162b2 BA.4/5 bivalent booster for XBB-related infections compared with BA.4/5-related infections was 56% (95% CI 12-78) versus 40% (27-50) for hospital admission; 34% (21-45) versus 36% (30-41) against emergency department or urgent care visits; and 29% (19-38) versus 27% (20-33) for outpatient encounters. INTERPRETATION: By mid-April, 2023, individuals previously vaccinated only with wild-type vaccines had little protection against COVID-19-including hospital admission. A BNT162b2 BA.4/5 bivalent booster restored protection against a range of COVID-19 outcomes, including against XBB-related sublineages, with the most substantial protection observed against hospital admission and critical illness. FUNDING: Pfizer.

Gait video-based prediction of unified Parkinson's disease rating scale score: a retrospective study.

BACKGROUND: The diagnosis of Parkinson's disease (PD) and evaluation of its symptoms require in-person clinical examination. Remote evaluation of PD symptoms is desirable, especially during a pandemic such as the coronavirus disease 2019 pandemic. One potential method to remotely evaluate PD motor impairments is video-based analysis. In this study, we aimed to assess the feasibility of predicting the Unified Parkinson's Disease Rating Scale (UPDRS) score from gait videos using a convolutional neural network (CNN) model. METHODS: We retrospectively obtained 737 consecutive gait videos of 74 patients with PD and their corresponding neurologist-rated UPDRS scores. We utilized a CNN model for predicting the total UPDRS part III score and four subscores of axial symptoms (items 27, 28, 29, and 30), bradykinesia (items 23, 24, 25, 26, and 31), rigidity (item 22) and tremor (items 20 and 21). We trained the model on 80% of the gait videos and used 10% of the videos as a validation dataset. We evaluated the predictive performance of the trained model by comparing the model-predicted score with the neurologist-rated score for the remaining 10% of videos (test dataset). We calculated the coefficient of determination (R2) between those scores to evaluate the model's goodness of fit. RESULTS: In the test dataset, the R2 values between the model-predicted and neurologist-rated values for the total UPDRS part III score and subscores of axial symptoms, bradykinesia, rigidity, and tremor were 0.59, 0.77, 0.56, 0.46, and 0.0, respectively. The performance was relatively low for videos from patients with severe symptoms. CONCLUSIONS: Despite the low predictive performance of the model for the total UPDRS part III score, it demonstrated relatively high performance in predicting subscores of axial symptoms. The model approximately predicted the total UPDRS part III scores of patients with moderate symptoms, but the performance was low for patients with severe symptoms owing to limited data. A larger dataset is needed to improve the model's performance in clinical settings.

Rapid implementation of an emergency on-site CKRT dialysate production system during the COVID-19 pandemic.

BACKGROUND: On December 29, 2021, during the delta wave of the Coronavirus Disease 2019 (COVID-19) pandemic, the stock of premanufactured solutions used for continuous kidney replacement therapy (CKRT) at the University of New Mexico Hospital (UNMH) was nearly exhausted with no resupply anticipated due to supply chain disruptions. Within hours, a backup plan, devised and tested 18 months prior, to locally produce CKRT dialysate was implemented. This report describes the emergency implementation and outcomes of this on-site CKRT dialysate production system. METHODS: This is a single-center retrospective case series and narrative report describing and reporting the outcomes of the implementation of an on-site CKRT dialysate production system. All adults treated with locally produced CKRT dialysate in December 2021 and January 2022 at UNMH were included. CKRT dialysate was produced locally using intermittent hemodialysis machines, hemodialysis concentrate, sterile parenteral nutrition bags, and connectors made of 3-D printed biocompatible rigid material. Outcomes analyzed included dialysate testing for composition and microbiologic contamination, CKRT prescription components, patient mortality, sequential organ failure assessment (SOFA) scores, and catheter-associated bloodstream infections (CLABSIs). RESULTS: Over 13 days, 22 patients were treated with 3,645 L of locally produced dialysate with a mean dose of 20.0 mL/kg/h. Fluid sample testing at 48 h revealed appropriate electrolyte composition and endotoxin levels and bacterial colony counts at or below the lower limit of detection. No CLABSIs occurred within 7 days of exposure to locally produced dialysate. In-hospital mortality was 81.8% and 28-day mortality was 68.2%, though illness severity was high, with a mean SOFA score of 14.5. CONCLUSIONS: Though producing CKRT fluid with IHD machines is not novel, this report represents the first description of the rapid and successful implementation of a backup plan for local CKRT dialysate production at a large academic medical center in the U.S. during the COVID-19 pandemic. Though conclusions are limited by the retrospective design and limited sample size of our analysis, our experience could serve as a guide for other centers navigating similar severe supply constraints in the future.

Collaborative nowcasting of COVID-19 hospitalization incidences in Germany.

Real-time surveillance is a crucial element in the response to infectious disease outbreaks. However, the interpretation of incidence data is often hampered by delays occurring at various stages of data gathering and reporting. As a result, recent values are biased downward, which obscures current trends. Statistical nowcasting techniques can be employed to correct these biases, allowing for accurate characterization of recent developments and thus enhancing situational awareness. In this paper, we present a preregistered real-time assessment of eight nowcasting approaches, applied by independent research teams to German 7-day hospitalization incidences during the COVID-19 pandemic. This indicator played an important role in the management of the outbreak in Germany and was linked to levels of non-pharmaceutical interventions via certain thresholds. Due to its definition, in which hospitalization counts are aggregated by the date of case report rather than admission, German hospitalization incidences are particularly affected by delays and can take several weeks or months to fully stabilize. For this study, all methods were applied from 22 November 2021 to 29 April 2022, with probabilistic nowcasts produced each day for the current and 28 preceding days. Nowcasts at the national, state, and age-group levels were collected in the form of quantiles in a public repository and displayed in a dashboard. Moreover, a mean and a median ensemble nowcast were generated. We find that overall, the compared methods were able to remove a large part of the biases introduced by delays. Most participating teams underestimated the importance of very long delays, though, resulting in nowcasts with a slight downward bias. The accompanying prediction intervals were also too narrow for almost all methods. Averaged over all nowcast horizons, the best performance was achieved by a model using case incidences as a covariate and taking into account longer delays than the other approaches. For the most recent days, which are often considered the most relevant in practice, a mean ensemble of the submitted nowcasts performed best. We conclude by providing some lessons learned on the definition of nowcasting targets and practical challenges.

Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial.

PURPOSE: This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage. METHODS: TOP-ART, a randomized, blinded, placebo-controlled, phase IIa trial, was conducted at a London major trauma center in adult trauma patients who activated the major hemorrhage protocol. Participants received artesunate or placebo (2:1 randomization ratio) as an intravenous bolus dose (2.4 mg/kg or 4.8 mg/kg) within 4 h of injury. The safety outcome was the 28-day serious adverse event (SAE) rate. The primary efficacy outcome was the 48 h sequential organ failure assessment (SOFA) score. The per-protocol recruitment target was 105 patients. RESULTS: The trial was terminated after enrolment of 90 patients because of safety concerns. Eighty-three participants received artesunate (n = 54) or placebo (n = 29) and formed the safety population and 75 met per-protocol criteria (48 artesunate, 27 placebo). Admission characteristics were similar between groups (overall 88% male, median age 29 years, median injury severity score 22), except participants who received artesunate were more shocked (median base deficit 9 vs. 4.7, p = 0.042). SAEs occurred in 17 artesunate participants (31%) vs. 5 who received placebo (17%). Venous thromboembolic events (VTE) occurred in 9 artesunate participants (17%) vs. 1 who received placebo (3%). Superiority of artesunate was not supported by the 48 h SOFA score (median 5.5 artesunate vs. 4 placebo, p = 0.303) or any of the trial's secondary endpoints. CONCLUSION: Among critically ill trauma patients, artesunate is unlikely to improve organ dysfunction and might be associated with a higher VTE rate.

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Safety of monovalent and bivalent BNT162b2 mRNA COVID-19 vaccine boosters in at-risk populations in Israel: a large-scale, retrospective, self-controlled case series study.

BACKGROUND: COVID-19 continues to be a major health threat, particularly among at-risk groups, including individuals aged 60 years or older and people with particular medical conditions. Nevertheless, the absence of sufficient vaccine safety information is one of the key contributors to vaccine refusal. We aimed to assess the short-term safety profile of the BNT162b2 mRNA COVID-19 vaccine booster doses. METHODS: In this self-controlled case series study, we used a database of members of the largest health-care organisation in Israel. We analysed the medical records of individuals at risk of COVID-19 complications who had received two doses of the monovalent BNT162b2 mRNA COVID-19 vaccine (tozinameran, Pfizer-BioNTech) as their primary course of vaccination and then also received BNT162b2 mRNA COVID-19 vaccine boosters between July 30, 2021, and Nov 28, 2022, as a monovalent first or second booster, or as a bivalent first, second, or third booster, or a combination of these. We included individuals who had active membership of the health-care organisation and who were alive (excluding COVID-19 deaths) throughout the entire study period. We excluded individuals who, during the study period, were either not active Clalit Health Services members or died of non-COVID-19 causes, and those who were infected with COVID-19 during the 7-day period after vaccination. Individuals' at-risk status was assessed on the day before the baseline period started. The primary outcome was non-COVID-19 hospitalisation for 29 adverse events that might be associated with vaccination. For each adverse event, we compared the risk difference of hospitalisation during a 28-day pre-vaccination baseline period versus during a 28-day post-vaccination period, using a non-parametric percentile bootstrap method. FINDINGS: Of the 3 574 243 members of the health-care organisation, 1 073 110 received a first monovalent booster, 394 251 received a second monovalent booster, and 123 084 received a bivalent first, second, or third booster. Overall, we found no indication of an elevated risk of non-COVID-19 hospitalisation following administration of any of the booster vaccines (risk difference in events per 100 000 individuals: first monovalent booster -37·1 [95% CI -49·8 to -24·2]; second monovalent booster -37·8 [-62·2 to -13·2]; and bivalent booster -18·7 [-53·6 to 15·4]). Except for extremely rare elevated risks after the first monovalent booster-of myocarditis (risk difference 0·7 events per 100 000 individuals [95% CI 0·3-1·3]), seizures (2·2 [0·4-4·1]), and thrombocytopenia (2·6 [0·7-4·7])-we found no safety signals in other adverse events, including ischaemic stroke. INTERPRETATION: This study provides the necessary vaccine safety assurances for at-risk populations to receive timed roll-out booster vaccinations. These assurances could reduce vaccine hesitancy and increase the number of at-risk individuals who opt to become vaccinated, and thereby prevent the severe outcomes associated with COVID-19. FUNDING: Israel Science Foundation and Israel Precision Medicine Partnership programme.

Three to four mRNA COVID-19 vaccines in multiple sclerosis patients on immunosuppressive drugs: Seroconversion and variant neutralization.

BACKGROUND AND PURPOSE: An enhanced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen could improve humoral vaccine response in patients with multiple sclerosis (MS) treated by anti-CD20. The aim was to evaluate the serological response and the neutralizing activity after BNT162b2 primary and booster vaccination in MS patients, including patients on anti-CD20 receiving a primary vaccine regimen enhanced with three injections. METHODS: In this prospective longitudinal cohort study of 90 patients (47 on anti-CD20, 10 on fingolimod, 33 on natalizumab, dimethylfumarate or teriflunomide), anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G antibodies were quantified and their neutralization capacity was evaluated by enzyme-linked immunosorbent assay (GenScript) and a virus neutralization test against B.1 historical strain, Delta and Omicron variants, before and after three to four BNT162b2 injections. RESULTS: After the primary vaccination scheme, the anti-RBD positivity rate was strongly decreased in patients on anti-CD20 (28% [15%; 44%] after two shots, 45% [29%; 62%] after three shots) and fingolimod (50% [16%; 84%]) compared to other treatments (100% [90%; 100%]). Neutralization activity was also decreased in patients on anti-CD20 and fingolimod, and notably low for the Omicron variant in all patients (0%-22%). Delayed booster vaccination was performed in 54 patients, leading to a mild increase of anti-RBD seropositivity in patients on anti-CD20 although it was still lower compared to other treatments (65% [43%; 84%] vs. 100% [87%; 100%] respectively). After a booster, Omicron neutralization activity remained low on anti-CD20 and fingolimod treated patients but was strongly increased in patients on other treatments (91% [72%; 99%]). DISCUSSION: In MS patients on anti-CD20, an enhanced primary vaccination scheme moderately increased anti-RBD seropositivity and anti-RBD antibody titre, but neutralization activity remained modest even after a fourth booster injection. TRIAL REGISTRATION INFORMATION: COVIVAC-ID, NCT04844489, first patient included on 20 April 2021.

Factors associated with COVID-19 length of hospitalization and mortality during four epidemic waves, March 2020–November 2021, Suriname

[ABSTRACT]. Objective. To determine the sociodemographic risk factors associated with coronavirus disease 2019 (COVID- 19) mortality in Suriname. Methods. This was a retrospective cohort study. All registered deaths from COVID-19 in Suriname (n=1112) between March 13, 2020 and November 11, 2021 were included. Data were collected from medical records and included demographic variables and hospitalization duration of patients who died. Descriptive statistics, chi-squared tests, ANOVA models, and logistic regression analyses were used to determine associations between sociodemographic variables, length of hospitalization, and mortality during four epidemic waves. Results. The case fatality rate over the study period was 22 per 1 000 population. The first epidemic wave was from July to August 2020, the second from December 2020 to January 2021, the third from May to June 2021, and the fourth from August to September 2021. Significant differences were found in the number of deaths and hospitalization duration by wave (p<0.001). Patients were more likely to have a longer hospitalization during the first (OR 1.66; 95% CI: 0.98, 2.82) and third waves (OR 2.37; 95% CI: 1.71, 3.28) compared with the fourth wave. Significant differences in mortality were also seen between ethnicities by wave (p=0.010). Compared with the mixed and other group, people of Creole ethnicity (OR 2.7; 95% CI: 1.33, 5.29) and Tribal people (OR 2.8; 95% CI: 1.12, 7.02) were more likely to die during the fourth wave than the third wave. Conclusions. Tailored interventions are needed for males, people of Creole descent, Tribal and Indigenous peoples, and people older than 65 years.

[RESUMEN]. Objetivo. Determinar los factores de riesgo sociodemográficos asociados a la mortalidad por la enfermedad por el coronavirus del 2019 (COVID-19) en Suriname. Métodos. Este fue un estudio de cohortes retrospectivo. Se analizaron todas las muertes por COVID-19 reg- istradas en Suriname (n=1112) entre el 13 de marzo del 2020 y el 11 de noviembre del 2021. Los datos se recopilaron a partir de los expedientes médicos, e incluyeron las variables demográficas y la duración de la hospitalización de los pacientes fallecidos. Se utilizaron métodos estadísticos descriptivos, la prueba de la ji al cuadrado, modelos de análisis de la varianza y análisis de regresión logística para determinar las asocia- ciones entre las variables sociodemográficas, la duración de la hospitalización y la mortalidad durante cuatro oleadas epidémicas. Resultados. La tasa de letalidad en el período del estudio fue de 22 por cada 1 000 habitantes. La primera oleada epidémica fue de julio a agosto del 2020; la segunda, de diciembre del 2020 a enero del 2021; la tercera, de mayo a junio del 2021; y la cuarta, de agosto a septiembre del 2021. Se observaron diferencias significativas en el número de muertes y la duración de la hospitalización entre las oleadas (p<0,001). Fue más probable que los pacientes tuvieran una hospitalización más prolongada durante la primera oleada (razón de posibilidades [odds ratio, OR] 1,66; IC del 95%: 0,98, 2,82) y la tercera (OR 2,37; IC del 95%: 1,71, 3,28) en comparación con la cuarta. También se observaron diferencias significativas en la mortalidad entre etnias según la oleada (p=0,010). En comparación con el grupo poblacional de origen mixto y de otro origen, las personas de la etnia criolla (OR 2,7; IC del 95%: 1,33, 5,29) y de origen tribal (OR 2,8; IC del 95%: 1,12, 7,02) tuvieron una mayor probabilidad de fallecer durante la cuarta oleada que durante la tercera. Conclusiones. Es preciso llevar a cabo intervenciones diseñadas específicamente para los hombres, las personas de ascendencia criolla, los pueblos tribales e indígenas y las personas mayores de 65 años.

[RESUMO]. Objetivo. Determinar os fatores de risco sociodemográficos associados à mortalidade por doença pelo coro- navírus 2019 (COVID-19) no Suriname. Métodos. Este foi um estudo de coorte retrospectivo. Foram incluídos todos os óbitos por COVID-19 registra- dos no Suriname (n=1112) entre 13 de março de 2020 e 11 de novembro de 2021. Os dados foram coletados de registros médicos e incluíram variáveis demográficas e a duração da internação dos pacientes que mor- reram. Estatísticas descritivas, testes de qui-quadrado, modelos de ANOVA e análises de regressão logística foram usados para determinar associações entre variáveis sociodemográficas, a duração da internação e a mortalidade durante quatro ondas epidêmicas. Resultados. A taxa de letalidade durante o período do estudo foi de 22 por 1 000 habitantes. A primeira onda epidêmica ocorreu de julho a agosto de 2020, a segunda, de dezembro de 2020 a janeiro de 2021, a terceira, de maio a junho de 2021 e a quarta, de agosto a setembro de 2021. Foram encontradas diferenças signifi- cativas no número de mortes e na duração da internação entre as ondas (p<0,001). Os pacientes tinham maior probabilidade de ter uma internação mais longa na primeira (razão de chances [RC]: 1,66; intervalo de confiança (IC 95%): 0,98–2,82) e na terceira onda (RC: 2,37; IC 95%: 1,71–3,28) em comparação com a quarta. Também foram observadas diferenças significativas entre etnias na mortalidade por onda (p=0,010). Em comparação com o grupo misto e outros, as pessoas de etnia crioula (RC: 2,7; IC 95%: 1,33–5,29) e tribal (RC: 2,8; IC 95%: 1,12–7,02) tinham maior probabilidade de morrer na quarta onda do que na terceira onda. Conclusões. São necessárias intervenções adaptadas para homens, pessoas de descendência crioula, povos tribais e indígenas e pessoas com mais de 65 anos.

Convalescent plasma for people with COVID-19: a living systematic review.

BACKGROUND: Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required. OBJECTIVES: To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19; and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS: To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, and the Epistemonikos COVID-19 L*OVE Platform. We searched monthly until 03 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating convalescent plasma for COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies we used RoB 2. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality at up to day 28, worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life, grade 3 or 4 adverse events, and serious adverse events. MAIN RESULTS: In this fourth review update version, we included 33 RCTs with 24,861 participants, of whom 11,432 received convalescent plasma. Of these, nine studies are single-centre studies and 24 are multi-centre studies. Fourteen studies took place in America, eight in Europe, three in South-East Asia, two in Africa, two in western Pacific and three in eastern Mediterranean regions and one in multiple regions. We identified a further 49 ongoing studies evaluating convalescent plasma, and 33 studies reporting as being completed. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease 29 RCTs investigated the use of convalescent plasma for 22,728 participants with moderate to severe disease. 23 RCTs with 22,020 participants compared convalescent plasma to placebo or standard care alone, five compared to standard plasma and one compared to human immunoglobulin. We evaluate subgroups on detection of antibodies detection, symptom onset, country income groups and several co-morbidities in the full text. Convalescent plasma versus placebo or standard care alone Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 220 per 1000; 21 RCTs, 19,021 participants; high-certainty evidence). It has little to no impact on need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.97 to 1.11; 296 per 1000; 6 RCTs, 14,477 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 665 per 1000; 6 RCTs, 12,721 participants; high-certainty evidence). Convalescent plasma may have little to no impact on quality of life (MD 1.00, 95% CI -2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). Convalescent plasma may have little to no impact on the risk of grades 3 and 4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 212 per 1000; 6 RCTs, 2392 participants; low-certainty evidence). It has probably little to no effect on the risk of serious adverse events (RR 1.14, 95% CI 0.91 to 1.44; 135 per 1000; 6 RCTs, 3901 participants; moderate-certainty evidence). Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces or increases all-cause mortality at up to day 28 (RR 0.73, 95% CI 0.45 to 1.19; 129 per 1000; 4 RCTs, 484 participants; very low-certainty evidence). We are uncertain whether convalescent plasma reduces or increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 311 per 1000; 1 study, 34 participants; very low-certainty evidence) and whether it reduces or increases the risk of serious adverse events (RR 0.80, 95% CI 0.55 to 1.15; 236 per 1000; 3 RCTs, 327 participants; very low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus human immunoglobulin Convalescent plasma may have little to no effect on all-cause mortality at up to day 28 (RR 1.07, 95% CI 0.76 to 1.50; 464 per 1000; 1 study, 190 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease We identified two RCTs reporting on 536 participants, comparing convalescent plasma to placebo or standard care alone, and two RCTs reporting on 1597 participants with mild disease, comparing convalescent plasma to standard plasma. Convalescent plasma versus placebo or standard care alone We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (odds ratio (OR) 0.36, 95% CI 0.09 to 1.46; 8 per 1000; 2 RCTs, 536 participants; very low-certainty evidence). It may have little to no effect on admission to hospital or death within 28 days (RR 1.05, 95% CI 0.60 to 1.84; 117 per 1000; 1 RCT, 376 participants; low-certainty evidence), on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 483 per 1000; 1 RCT, 376 participants; low-certainty evidence), on the risk of grades 3 and 4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 144 per 1000; 1 RCT, 376 participants; low-certainty evidence) and the risk of serious adverse events (RR 1.14, 95% CI 0.66 to 1.94; 133 per 1000; 1 RCT, 376 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (OR 0.30, 95% CI 0.05 to 1.75; 2 per 1000; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.49, 95% CI 0.31 to 0.75; 36 per 1000; 2 RCTs, 1595 participants; moderate-certainty evidence). Convalescent plasma may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.98 to 1.27; 1 RCT, 416 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. This is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence. AUTHORS' CONCLUSIONS: For the comparison of convalescent plasma versus placebo or standard care alone, our certainty in the evidence that convalescent plasma for individuals with moderate to severe disease does not reduce mortality and has little to no impact on clinical improvement or worsening is high. It probably has little to no effect on SAEs. For individuals with mild disease, we have very-low to low certainty evidence for most primary outcomes and moderate certainty for hospital admission or death. There are 49 ongoing studies, and 33 studies reported as complete in a trials registry. Publication of ongoing studies might resolve some of the uncertainties around convalescent plasma therapy for people with asymptomatic or mild disease.