Identifying patterns of reported findings on long-term cardiac complications of COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Prior reviews synthesized findings of studies on long-term cardiac complications of COVID-19. However, the reporting and methodological quality of these studies has not been systematically evaluated. Here, we conducted a systematic review and meta-analysis on long-term cardiac complications of COVID-19 and examined patterns of reported findings by study quality and characteristics. METHODS: We searched for studies examining long-term cardiac complications of COVID-19 that persisted for 4 weeks and over. A customized Newcastle-Ottawa scale (NOS) was used to evaluate the quality of included studies. Meta-analysis was performed to generate prevalence estimates of long-term cardiac complications across studies. Stratified analyses were further conducted to examine the prevalence of each complication by study quality and characteristics. The GRADE approach was used to determine the level of evidence for complications included in the meta-analysis. RESULTS: A total number of 150 studies describing 57 long-term cardiac complications were included in this review, and 137 studies reporting 17 complications were included in the meta-analysis. Only 25.3% (n = 38) of studies were of high quality based on the NOS quality assessment. Chest pain and arrhythmia were the most widely examined long-term complications. When disregarding study quality and characteristics, summary prevalence estimates for chest and arrhythmia were 9.79% (95% CI 7.24-13.11) and 8.22% (95% CI 6.46-10.40), respectively. However, stratified analyses showed that studies with low-quality scores, small sample sizes, unsystematic sampling methods, and cross-sectional design were more likely to report a higher prevalence of complications. For example, the prevalence of chest pain was 22.17% (95% CI 14.40-32.55), 11.08% (95% CI 8.65-14.09), and 3.89% (95% CI 2.49-6.03) in studies of low, medium, and high quality, respectively. Similar patterns were observed for arrhythmia and other less examined long-term cardiac complications. CONCLUSION: There is a wide spectrum of long-term cardiac complications of COVID-19. Reported findings from previous studies are strongly related to study quality, sample sizes, sampling methods, and designs, underscoring the need for high-quality epidemiologic studies to characterize these complications and understand their etiology.

Risk management actions following genetic testing in the Cancer Health Assessments Reaching Many (CHARM) Study: A prospective cohort study.

BACKGROUND: Genetic testing can identify cancer risk early, enabling prevention and early detection. We describe use of risk management interventions following genetic testing in the Cancer Health Assessment Reaching Many (CHARM) study. CHARM assessed risk and provided genetic testing to low income, low literacy, and other underserved populations that historically face barriers to accessing cancer genetic services. METHODS: CHARM was implemented in Kaiser Permanente Northwest (KPNW) and Denver Health (DH) between 2018 and 2020. We identified post-testing screening (mammography, breast MRI, colonoscopy) and surgical (mastectomy, oophorectomy) procedures using electronic health records. We examined utilization in participants who did and did not receive actionable risk management recommendations from study genetic counselors following national guidelines. RESULTS: CHARM participants were followed for an average of 15.4 months (range: 0.4-27.8 months) after results disclosure. Less than 2% (11/680) received actionable risk management recommendations (i.e., could be completed in the initial years following testing) based on their test result. Among those who received actionable recommendations, risk management utilization was moderate (54.5%, 6/11 completed any procedure) and varied by procedure (mammogram: 0/3; MRI: 2/4; colonoscopy: 4/5; mastectomy: 1/5; oophorectomy: 0/3). Cancer screening and surgery procedures were rare in participants without actionable recommendations. CONCLUSION: Though the number of participants who received actionable risk management recommendations was small, our results suggest that implementing CHARM's risk assessment and testing model increased access to evidence-based genetic services and provided opportunities for patients to engage in recommended preventive care, without encouraging risk management overuse.

COVID-19 related change in breast cancer diagnosis, stage, treatment, and case volume: 2019-2021.

PURPOSE: Evaluate the COVID-19 pandemic impact on breast cancer detection method, stage and treatment before, during and after health care restrictions. METHODS: In a retrospective tertiary cancer care center cohort, first primary breast cancer (BC) patients, years 2019-2021, were reviewed (n = 1787). Chi-square statistical comparisons of detection method (patient (PtD)/mammography (MamD), Stage (0-IV) and treatment by pre-pandemic time 1: 2019 + Q1 2020; peak-pandemic time 2: Q2-Q4 2020; pandemic time 3: Q1-Q4 2021 (Q = quarter) periods and logistic regression for odds ratios were used. RESULTS: BC case volume decreased 22% in 2020 (N = 533) (p = .001). MamD declined from 64% pre-pandemic to 58% peak-pandemic, and increased to 71% in 2021 (p < .001). PtD increased from 30 to 36% peak-pandemic and declined to 25% in 2021 (p < .001). Diagnosis of Stage 0/I BC declined peak-pandemic when screening mammography was curtailed due to lock-down mandates but rebounded above pre-pandemic levels in 2021. In adjusted regression, peak-pandemic stage 0/I BC diagnosis decreased 24% (OR = 0.76, 95% CI: 0.60, 0.96, p = .021) and increased 34% in 2021 (OR = 1.34, 95% CI: 1.06, 1.70, p = .014). Peak-pandemic neoadjuvant therapy increased from 33 to 38% (p < .001), primarily for surgical delay cases. CONCLUSIONS: The COVID-19 pandemic restricted health-care access, reduced mammography screening and created surgical delays. During the peak-pandemic time, due to restricted or no access to mammography screening, we observed a decrease in stage 0/I BC by number and proportion. Continued low case numbers represent a need to re-establish screening behavior and staffing.

Longitudinal adherence to breast cancer surveillance following cancer genetic testing in an integrated health care system.

PURPOSE: Screening with mammography and breast magnetic resonance imaging (MRI) is an important risk management strategy for individuals with inherited pathogenic variants (PVs) in genes associated with increased breast cancer risk. We describe longitudinal screening adherence in individuals who underwent cancer genetic testing as part of usual care in a vertically integrated health system. METHODS: We determined the proportion time covered (PTC) by annual mammography and breast MRI for individuals with PVs in TP53, BRCA1, BRCA2, PALB2, NF1, CHEK2, and ATM. We determined time covered by biennial mammography beginning at age 50 years for individuals who received negative results, uncertain results, or with PVs in genes without specific breast cancer screening recommendations. RESULTS: One hundred and forty individuals had PVs in TP53, BRCA1, BRCA2, PALB2, NF1, CHEK2, or ATM. Among these individuals, average PTC was 48% (range 0-99%) for annual screening mammography and 34% (range 0-100%) for annual breast MRI. Average PTC was highest for individuals with PVs in CHEK2 (N = 14) and lowest for individuals with PVs in TP53 (N = 3). Average PTC for biennial mammography (N = 1,027) was 49% (0-100%). CONCLUSION: Longitudinal screening adherence in individuals with PVs in breast cancer associated genes, as measured by the proportion of time covered, is low; adherence to annual breast MRI falls below that of annual mammography. Additional research should examine screening behavior in individuals with PVs in breast cancer associated genes with a goal of developing interventions to improve adherence to recommended risk management.

OsWRKY76 positively regulates drought stress via OsbHLH148-mediated jasmonate signaling in rice.

Drought stress is a major environmental threat that limits plant growth and crop productivity. Therefore, it is necessary to uncover the molecular mechanisms behind drought tolerance in crops. Here, OsWRKY76 positively regulated drought stress in rice. OsWRKY76 expression was induced by PEG treatment, dehydration stress, and exogenous MeJA rather than by no treatment. Notably, OsWRKY76 knockout weakened drought tolerance at the seedling stage and decreased MeJA sensitivity. OsJAZ12 was significantly induced by drought stress, and its expression was significantly higher in OsWRKY76-knockout mutants than in wild-type ZH11 under drought stress. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that OsWRKY76 interacted with OsJAZ12. OsWRKY76 weakened the interaction between OsbHLH148 and OsJAZ12 in yeast cells. The OsJAZ12 protein repressed the transactivation activity of OsbHLH148, and this repression was partly restored by OsWRKY76 in rice protoplasts. Moreover, OsDREB1E expression was lower in OsWRKY76-knockout mutants than in wild-type ZH11 under drought stress, but it was upregulated under normal growth conditions. Yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase assays showed that OsWRKY76 and OsbHLH148 bound directly to the OsDREB1E promoter and activated OsDREB1E expression in response to drought stress. These results suggest that OsWRKY76 confers drought tolerance through OsbHLH148-mediated jasmonate signaling in rice, offering a new clue to uncover the mechanisms behind drought tolerance.

Long-term cardiac symptoms following COVID-19: a systematic review and meta-analysis.

Background: There is growing body of literature on the long-term cardiac symptoms following COVID-19. We conducted a systematic review and meta-analysis to synthesize and evaluate related evidence to inform clinical management and future studies. Methods: We searched two preprint and seven peer-reviewed article databases from January 1, 2020 to January 8, 2022 for studies investigating cardiac symptoms that persisted for at least 4 weeks among individuals who survived COVID-19. A customized Newcastle-Ottawa scale was used to evaluate the quality of included studies. Random-effects meta-analyses were performed to estimate the proportion of symptoms with 95% confidence intervals (CI), and stratified analyses were conducted to quantify the proportion of symptoms by study characteristics and quality. Results: A total of 101 studies describing 49 unique long-term cardiac symptoms met the inclusion criteria. Based on quality assessment, only 15.8% of the studies (n=16) were of high quality, and most studies scored poorly on sampling representativeness. The two most examined symptoms were chest pain and arrhythmia. Meta-analysis showed that the proportion of chest pain was 10.1% (95% CI: 6.4-15.5) and arrhythmia was 9.8% (95% CI: 5.4-17.2). Stratified analyses showed that studies with low-quality score, small sample size, unsystematic sampling method, and cross-sectional design were most likely to report high proportions of symptoms. For example, the proportion of chest pain was 21.3% (95% CI: 10.5-38.5), 9.3% (95% CI: 6.0-14.0), and 4.0% (95% CI: 1.3-12.0) in studies with low, medium, and high-quality scores, respectively. Similar patterns were observed for other cardiac symptoms including hypertension, cardiac abnormalities, myocardial injury, thromboembolism, stroke, heart failure, coronary disease, and myocarditis. Discussion: There is a wide spectrum of long-term cardiac symptoms following COVID-19. Findings of existing studies are strongly related to study quality, size and design, underscoring the need for high-quality epidemiologic studies to characterize these symptoms and understand their etiology.

OsWRKY28 positively regulates salinity tolerance by directly activating OsDREB1B expression in rice.

KEY MESSAGE: OsWRKY28 confers salinity tolerance by directly binding to OsDREB1B promoter and increasing its transcriptional activity, and negatively regulates abscisic acid mediated seedling establishment in rice. WRKY transcription factors have been reported to play a vital role in plants growth, development, abiotic and biotic stress responses. In this study, we explored the functions of a transcription factor OsWRKY28 in rice. The transcript level of OsWRKY28 was strikingly increased under drought, chilling, salt and abscisic acid treatments. The OsWRKY28 overexpression lines showed enhanced salinity stress tolerance, whereas the oswrky28 mutants displayed salt sensitivity compared to wild-type plants. Under salt stress treatment, the expression levels of OsbZIP05, OsHKT1;1 and OsDREB1B were significantly lower yet the level of OsHKT2;1 was significantly higher in oswrky28 mutants than those in wide type plants. Our data of yeast one-hybrid assay and dual-luciferase assay supported that OsWRKY28 could directly bind to the promoter of OsDREB1B to enhance salinity tolerance in rice. In addition, OsWRKY28 overexpression lines displayed hyposensitivity and the oswrky28 mutants showed hypersensitivity compared to wild-type plants under exogenous abscisic acid treatment. Based on the results of yeast two-hybrid assay and GAL4-dependent chimeric transactivation assay, OsWRKY28 physically interacts with OsMPK11 and its transcriptional activity could be regulated by OsMPK11. Together, OsWRKY28 confers salinity tolerance through directly targeting OsDREB1B promoter and further activating its transcription in rice.

Trastuzumab therapy duration in HER2-positive de novo metastatic breast cancer: 1999-2018.

PURPOSE: The optimal duration of first-line trastuzumab (T) treatment for de novo stage IV HER2-positive metastatic breast cancer (MBC) patients after complete response (CR) is not known. METHODS: A retrospective cohort study of de novo stage IV HER2-positive MBC patients who had trastuzumab included in their initial treatment (n = 69), 1999-2018, was conducted with follow-up for CR, progressive disease (PD), vital status, and disease-specific survival (DSS). Statistics included Kaplan-Meier plots and Cox proportional hazards models. RESULTS: Mean trastuzumab treatment time was 4.1 years (range 0.1-15). 54% of patients experienced CR at average time 9 months on treatment (n = 37). Eight CR patients discontinued T treatment after 18 months average post-CR time (range 0-86) and twenty-nine stayed on T treatment post CR [average 65 months (range 10-170)]. Average follow-up was 6 years, range 1-15 years. 5-year DSS was 92% for CR on T patients (N = 29); 88% CR off T (n = 8); 73% No CR on T (n = 14); and 29% No CR off T (n = 18) (p < 0.001). In forward Cox proportional hazards modeling, CR = yes [HzR = 0.31, (95% CI 0.14, 0.73), p = 0.007], continuous T treatment > 2 years [HzR = 0.24, (95% CI 0.10, 0.62), p = 0.003], and age < 65 [HzR = 0.29, (95% CI 0.11, 0.81), p = 0.018] were significantly associated with better DSS. CONCLUSION: Maximum trastuzumab treatment time to CR was 27 months with 2 or more years trastuzumab treatment independently associated with better survival. Survival comparisons and hazard modeling both indicate as good or better survival associated with continuous trastuzumab treatment regardless of CR status. Word count (n = 250).

Risk-reducing surgery in unaffected individuals receiving cancer genetic testing in an integrated health care system.

BACKGROUND: Germline genetic testing enables primary cancer prevention, including through prophylactic surgery. We examined risk-reducing surgeries in unaffected individuals tested for hereditary cancer susceptibly between 2010 and 2018 in the Kaiser Permanente Northwest health system. METHODS: We used an internal genetic testing database to create a cohort of individuals who received tests including one or more high-penetrance hereditary cancer susceptibility gene. We then identified, after testing, bilateral mastectomy, bilateral salpingo-oophorectomy (BSO), and total hysterectomy procedures in electronic health record and claims data through 2019. We describe surgery utilization by genetic test results and National Comprehensive Cancer Network (NCCN) guidelines. RESULTS: The cohort included 1020 individuals, 16% with pathogenic/likely pathogenic (P/LP) variants in one or more of the following genes: BRCA1, BRCA2, CHEK2, APC, MUTYH, ATM, MSH2, PALB2, BRIP1, MLH1, MSH6, EPCAM, FLCN, RAD51C, RAD51D, or TP53. Among individuals with P/LP variants making them candidates for mastectomy, BSO, or hysterectomy per NCCN guidelines, 34% (33/97), 24% (23/94), and 8% (1/12), respectively, underwent surgery during follow-up. Fifty-three percent (18/37) of hysterectomies were among APC, BRCA1, and BRCA2 P/LP variant heterozygotes, typically concurrent with BSO. Three individuals with variants of uncertain significance (only) and 22 with negative results had prophylactic surgery after genetic testing. CONCLUSIONS: Uptake of risk-reducing surgery following usual care genetic testing appears to be lower than in studies that actively recruit high-risk patients and provide testing and follow-up care in specialized settings. Factors in addition to genetic test results and NCCN guidelines motivate prophylactic surgery use and deserve further study.

Case fatality risk of diarrhoeal pathogens: a systematic review and meta-analysis.

BACKGROUND: Estimates of the relative contribution of different pathogens to all-cause diarrhoea mortality are needed to inform global diarrhoea burden models and prioritize interventions. We aimed to investigate and estimate heterogeneity in the case fatality risk (CFR) of different diarrhoeal pathogens. METHODS: We conducted a systematic review and meta-analysis of studies that reported cases and deaths for 15 enteric pathogens published between 1990 and 2019. The primary outcome was the pathogen-specific CFR stratified by age group, country-specific under-5 mortality rate, setting, study year and rotavirus vaccine introduction status. We developed fixed-effects and multilevel mixed-effects logistic regression models to estimate the pooled CFR overall and for each pathogen, controlling for potential predictors of heterogeneity. RESULTS: A total of 416 studies met review criteria and were included in the analysis. The overall crude CFR for all pathogens was 0.65%, but there was considerable heterogeneity between and within studies. The overall CFR estimated from a random-effects model was 0.04% (95% CI: 0.026%-0.062%), whereas the pathogen-specific CFR estimates ranged from 0% to 2.7%. When pathogens were included as predictors of the CFR in the overall model, the highest and lowest odds ratios were found for enteropathogenic Escherichia coli (EPEC) [odds ratio (OR) = 3.0, 95% CI: 1.28-7.07] and rotavirus (OR = 0.23, 95% CI: 0.13-0.39), respectively. CONCLUSION: We provide comprehensive estimates of the CFR across different diarrhoeal pathogens and highlight pathogens for which more studies are needed. The results motivate the need for diarrhoeal interventions and could help prioritize pathogens for vaccine development.

Association Between Genetic Testing for Hereditary Breast Cancer and Contralateral Prophylactic Mastectomy Among Multiethnic Women Diagnosed With Early-Stage Breast Cancer.

PURPOSE: Increasing usage of multigene panel testing has identified more patients with pathogenic or likely pathogenic (P or LP) variants in low-moderate penetrance genes or variants of uncertain significance (VUS). Our study evaluates the association between genetic test results and contralateral prophylactic mastectomy (CPM) among patients with breast cancer. METHODS: We conducted a retrospective cohort study among women diagnosed with unilateral stage 0-III breast cancer between 2013 and 2020 who underwent genetic testing. We examined whether genetic test results were associated with CPM using multivariable logistic regression models. RESULTS: Among 707 racially or ethnically diverse women, most had benign or likely benign (B or LB) variants, whereas 12.5% had P or LP and 17.9% had VUS. Racial or ethnic minorities were twice as likely to receive VUS. Patients with P or LP variants had higher CPM rates than VUS or B or LB (64.8% v 25.8% v 25.9%), and highest among women with P or LP variants in high-penetrance genes (74.6%). On multivariable analysis, P or LP compared with B or LB variants were significantly associated with CPM (odds ratio = 4.24; 95% CI, 2.48 to 7.26). CONCLUSION: Women with P or LP variants on genetic testing were over four times more likely to undergo CPM than B or LB. Those with VUS had similar CPM rates as B or LB. Our findings suggest appropriate genetic counseling and communication of cancer risk to multiethnic breast cancer survivors.

Association Between Genetic Predictors for C-Reactive Protein and Venous Thromboembolism With Severe Adverse Coronavirus Disease 2019 Outcomes.

To assess if genetic predictors for C-reactive protein and risk of venous thromboembolism are associated with severe outcomes among individuals who tested positive for severe acute respiratory syndrome coronavirus 2. DESIGN: Retrospective cohort study. SETTING: U.K. Biobank. PATIENTS OR SUBJECTS: U.K. Biobank participants with European ancestry who were recorded to have a positive polymerase chain reaction test result for severe acute respiratory syndrome coronavirus 2 between March 16, 2020, and August 14, 2020. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: We constructed separate genetic risk scores for C-reactive protein and venous thromboembolism consisting of 56 and 37 genetic variants that have been significantly associated with venous thromboembolism and C-reactive protein, respectively. Among 1,126 individuals who were diagnosed with coronavirus disease 2019, 48% had a coronavirus disease 2019-related hospitalization, 16% received critical care support, 10% had critical respiratory support, and 21% died from coronavirus disease 2019. Genetic predisposition to high C-reactive protein concentrations was marginally associated with a lower risk of death from coronavirus disease 2019 (odds ratio, 0.85; 95% CI, 0.73-1.00; p = 0.05). No other associations were significant. CONCLUSIONS: Our results do not support associations between polygenic risk for elevated blood C-reactive protein concentrations or venous thromboembolism and severe coronavirus disease 2019 health outcomes. Thus, considering genetic predisposition associated with C-reactive protein concentrations or venous thromboembolism risk is not meaningful for predicting severe coronavirus disease 2019 health outcomes.

Association of enteropathogen detection with diarrhoea by age and high versus low child mortality settings: a systematic review and meta-analysis.

BACKGROUND: The odds ratio (OR) comparing pathogen presence in diarrhoeal cases versus asymptomatic controls is a measure for diarrhoeal disease cause that has been integrated into burden of disease estimates across diverse populations. This study aimed to estimate the OR describing the association between pathogen detection in stool and diarrhoea for 15 common enteropathogens by age group and child mortality setting. METHODS: We did a systematic review to identify case-control and cohort studies published from Jan 1, 1990, to July 9, 2019, which examined at least one enteropathogen of interest and the outcome diarrhoea. The analytical dataset included data extracted from published articles and supplemented with data from the Global Enteric Multicenter Study and the Malnutrition and Enteric Disease study. Random effects meta-analysis models were fit for each enteropathogen, stratified by age group and child mortality level, and adjusted for pathogen detection method and study design to produce summary ORs describing the association between pathogen detection in stool and diarrhoea. FINDINGS: 1964 records were screened and 130 studies (over 88 079 cases or diarrhoea samples and 135 755 controls or non-diarrhoea samples) were available for analysis. Heterogeneity (I2) in unadjusted models was substantial, ranging from 27·6% to 86·6% across pathogens. In stratified and adjusted models, summary ORs varied by age group and setting, ranging from 0·4 (95% CI 0·2-0·6) for Giardia lamblia to 54·1 (95% CI 7·4-393·5) for Vibrio cholerae. INTERPRETATION: Incorporating effect estimates from diverse data sources into diarrhoeal disease cause and burden of disease models is needed to produce more representative estimates. FUNDING: WHO, Bill & Melinda Gates Foundation, and National Institutes of Health.

Continued proportional age shift of confirmed positive COVID-19 incidence over time to children and young adults: Washington State March-August 2020.

BACKGROUND: As the coronavirus (COVID-19) epidemic passed initial infection peak in Washington State, phased re-opening lifted stay-at-home orders and restrictions leading to increased non-essential work, social activities and gathering, especially among younger persons. METHODS: A longitudinal cohort analysis of Washington State Department of Health COVID-19 confirmed case age distribution 1) March-April 2020 (N = 13,934) and 2) March-August 2020 (N = 76,032) for proportional change over time using chi square tests for significance. RESULTS: From March 1st to April 19, 2020 COVID-19 age distribution shifted with a 10% decline in cases age 60 years and older and a 20% increase in age 0-19/20-39 years (chi-square = 223.10, p < .001). Number of cases over the initial analysis period were 0-19 years n = 515, 20-39 years n = 4078, 40-59 years n = 4788, 60-79 years n = 3221, 80+ years n = 1332. After the peak (March 22, 2020), incidence declined in older age groups and increased among age 0-19 and 20-39 age groups from 20% to 40% of total cases by April 19 and 50% by May 3. During this time testing expanded with more testing among older age groups and less testing among younger age groups while case positivity shifted young. Percent positive cases age 0-19/20-39 years through August 2020 increased to a consistent average of 60% [age 0-19 increased to 19% (N = 10257), age 20-39 increased to 42% (N = 30215)]. CONCLUSIONS: An increased sustained proportion of COVID-19 incidence is present among children (age 0-19) and young adults (age 20-39) indicating an elevated role in disease spread during the epidemic creating a possible reservoir of disease with spillover risk to more vulnerable older persons and those with comorbid conditions. Media savvy age-appropriate messaging to enhance mitigation compliance among less vulnerable, more mobile and lower priority vaccination age groups will be a continued necessity and priority to reduce overall population incidence.

Sexual behaviour change following HIV testing services: a systematic review and meta-analysis.

INTRODUCTION: Learning one's HIV status through HIV testing services (HTS) is an essential step toward accessing treatment and linking to preventive services for those at high HIV risk. HTS may impact subsequent sexual behaviour, but the degree to which this varies by population or is true in the setting of contemporary HIV prevention activities is largely unknown. As part of the 2019 World Health Organization Consolidated Guidelines on HTS, we undertook a systematic review and meta-analysis to determine the effect of HTS on sexual behaviour. METHODS: We searched nine electronic databases for studies published between July 2010 and December 2019. We included studies that reported on at least one outcome (condom use [defined as the frequency of condom use or condom-protected sex], number of sex partners, HIV incidence, STI incidence/prevalence). We included studies that prospectively assessed outcomes and that fit into one of three categories: (1) those evaluating more versus less-intensive HTS, (2) those of populations receiving HTS versus not and (3) those evaluating outcomes after versus before HTS. We conducted meta-analyses using random-effects models. RESULTS AND DISCUSSION: Of 29 980 studies screened, 76 studies were included. Thirty-eight studies were randomized controlled trials, 36 were cohort studies, one was quasi-experimental and one was a serial cross-sectional study. There was no significant difference in condom use among individuals receiving more-intensive HTS compared to less-intensive HTS (relative risk [RR]=1.03; 95% CI: 0.99 to 1.07). Condom use was significantly higher after receiving HTS compared to before HTS for individuals newly diagnosed with HIV (RR = 1.65; 95% CI: 1.36 to 1.99) and marginally significantly higher for individuals receiving an HIV-negative diagnosis (RR = 1.63; 95% CI: 1.01 to 2.62). Individuals receiving more-intensive HTS reported fewer sex partners at follow-up than those receiving less-intensive HTS, but the finding was not statistically significant (mean difference = -0.28; 95% CI: -3.66, 3.10). CONCLUSIONS: Our findings highlight the importance of using limited resources towards HTS strategies that focus on early HIV diagnosis, treatment and prevention services rather than resources dedicated to supplementing or enhancing HTS with additional counselling or other interventions.