Cervical cancer screening improvements with self- sampling during the COVID-19 pandemic

BackgroundAt the onset of the COVID-19 pandemic cervical screening in the capital region of Sweden was cancelled for several months. A series of measures to preserve and improve the cervical screening under the circumstances were instituted, including a switch to screening with HPV self-sampling to enable screening in compliance with social distancing recommendations. MethodsWe describe the major changes implemented, which were i) nationwide implementation of HPV screening ii) switch to primary self-sampling instead of clinician sampling iii) implementation of HPV screening in all screening ages and iv) combined HPV vaccination and HPV screening in the cervical screening program. ResultsA temporary government regulation allowed primary self-sampling with HPV screening in all ages. In the Stockholm region, 330,000 self-sampling kits were sent to the home address of screening-eligible women, instead of an invitation to clinician sampling. An increase in population test coverage was seen (from 66% to 70% in just one year). In addition, a national campaign for faster elimination of cervical cancer with concomitant screening and vaccination for women in ages 23-28 was launched. ConclusionsThe COVID-19 pandemic necessitated major changes in the cervical cancer preventive strategies, where it can already be concluded that the strategy with organised primary self-sampling for HPV has resulted in a major improvement of population test-coverage. FundingFunded by the Swedish Association of Local Authorities and Regions, the Swedish Cancer Society, the European Unions Horizon 2020 Research and Innovation Program, the Swedish government and the Stockholm county.

Predicting past and future SARS-CoV-2-related sick leave using discrete time Markov modelling

BackgroundPrediction of SARS-CoV-2-induced sick leave among healthcare workers (HCWs) is essential for being able to plan the healthcare response to the epidemic. MethodsDuring first wave of the SARS-Cov-2 epidemic (April 23rd to June 24th, 2020), the HCWs in the greater Stockholm region in Sweden were invited to a study of past or present SARS-CoV-2 infection. We develop a discrete time Markov model using a cohort of 9449 healthcare workers (HCWs) who had complete data on SARS-CoV-2 RNA and antibodies as well as sick leave data for the calendar year 2020. The one-week and standardized longer term transition probabilities of sick leave and the ratios of the standardized probabilities for the baseline covariate distribution were compared with the referent period (an independent period when there were no SARS-CoV-2 infections) in relation to PCR results, serology results and gender. ResultsThe one-week probabilities of transitioning from healthy to partial sick leave or full sick leave during the outbreak as compared to after the outbreak were highest for healthy HCWs testing positive for large amounts of virus (3.69, (95% confidence interval, CI: 2.44-5.59) and 6.67 (95% CI: 1.58-28.13), respectively). The proportion of all sick leaves attributed to COVID-19 during outbreak was at most 55% (95% CI: 50%-59%). ConclusionsA robust Markov model enabled use of simple SARS-CoV-2 testing data for quantifying past and future COVID-related sick leave among HCWs, which can serve as a basis for planning of healthcare during outbreaks.

Feasibility of sending a direct send HPV self-sampling kit to long-term non-attenders in an organized cervical screening program.

INTRODUCTION: Non-participation in screening is a main risk factor for cervical cancer. Human-papillomavirus (HPV) self-sampling may be an alternative to repeated invitations for non-attenders. Several studies have concluded that participation among non-attenders increases significantly when offering self-sampling kits for HPV. However, participation rates are highly variable between settings, and therefore pilots to determine optimal implementation strategy have been recommended before routine roll out. MATERIALS AND METHODS: All women who had not participated in the organized screening program for at least 10 years aged 33-62 in one Swedish county were identified through screening registers. HPV self-sampling kits were sent to all eligible women. Participation was defined as returning a self-sample kit or attending routine screening within 6 months. Women who did not submit the kit within 8 weeks were randomized to receive a written reminder. HPV-positive women were referred directly to colposcopy without prior triage. Biopsies for histopathologic confirmation were used as gold standard. RESULTS: Among eligible women, 150/741 (20.2%) returned the self-sample kit or attended routine screening. A randomized written reminder was sent out to 319/591 non-responders and another 11 women returned the kit. In total, 23/147 (16.3%) of returned kits were HPV positive. Out of the 23 HPV-positive women, 17 (74%) attended colposcopy; 10/17 (59%) had a histopathological high-grade squamous intraepithelial lesions (HSIL) or cervical cancer. The most common HPV type was HPV 52, and 2 out of 3 women with HPV 16 had a histopathologically confirmed cancer. CONCLUSION: The direct send kit strategy and referral of all HPV-positive women to colposcopy without prior triage appears to be feasible if resources are available and should be prioritized given the high prevalence of HSIL lesions and cancer among non-attenders. A written reminder might further increase attendance.

SARS-CoV-2 infections amongst personnel providing home care services for older persons in Stockholm, Sweden.

BACKGROUND: In Sweden, home care services is a major external contact for older persons. METHODS: Five home care service companies in Stockholm, Sweden, enrolled 405 employees to a study including serum IgG to SARS-CoV-2 and SARS-CoV-2 virus in throat swabs. RESULTS: 20.1% (81/403) of employees were seropositive, about twice as many as in a simultaneously enrolled reference population (healthcare workers entirely without patient contact, n = 3671; 9.7% seropositivity). 13/379 employees (3.4%) had a current infection (PCR positivity). Amongst these, 5 were also seropositive and 3 were positive with low amounts of virus. High amounts of virus and no antibodies (a characteristic for presymptomatic COVID-19) were present in 5 employees (1.3%). CONCLUSIONS: Personnel providing home services for older persons appear to be a risk group for SARS-CoV-2. Likely presymptomatic employees can be readily identified by screening. Increased protection of employees and of the older persons they serve is warranted.

Differences in risk for SARS-CoV-2 infection among healthcare workers

Healthcare workers (HCWs) are a risk group for SARS-CoV-2 infection, but which healthcare work that conveys risk and to what extent such risk can be prevented is not clear. Starting on April 24th, 2020, all employees at work (n=15,300) at the Karolinska University Hospital, Stockholm, Sweden were invited and 92% consented to participate in a SARS-CoV-2 cohort study. Complete SARS-CoV-2 serology was available for n=12,928 employees and seroprevalences were analyzed by age, sex, profession, patient contact, and hospital department. Relative risks were estimated to examine the association between type of hospital department as a proxy for different working environment exposure and risk for seropositivity, adjusting for age, sex, sampling week, and profession. Wards that were primarily responsible for COVID-19 patients were at increased risk (adjusted OR 1.95 (95% CI 1.65-2.32) with the notable exception of the infectious diseases and intensive care units (adjusted OR 0.86 (95% CI 0.66-1.13)), that were not at increased risk despite being highly exposed. Several units with similar types of work varied greatly in seroprevalences. Among the professions examined, nurse assistants had the highest risk (adjusted OR 1.62 (95% CI 1.38-1.90)). Although healthcare workers, in particular nurse assistants, who attend to COVID-19 patients are a risk group for SARS-CoV-2 infection, several units caring for COVID-19 patients had no excess risk. Large variations in seroprevalences among similar units suggest that healthcare work-related risk of SARS-CoV-2 infection may be preventable.

SARS-CoV-2 infections among personnel providing home care services for the elderly in Stockholm, Sweden

BackgroundIn March 2020, Stockholm, Sweden was hit by a severe outbreak of SARS-CoV-2. Four weeks later, a systematic study of testing for past or present infections among healthcare workers in the region was launched. Only a minority of COVID-19 related deaths occurred at hospitals and the study was therefore extended to employees in companies providing home care services for the elderly. MethodsFive companies offered participation to 438 employees at work and 405 employees (92.5%) were enrolled. Serum samples were analyzed for IgG to SARS-CoV-2 and throat swabs were tested by for the SARS-CoV-2 virus by PCR. ResultsAmong home care employees, 20.1% (81/403) were seropositive, about twice as many as in a simultaneously enrolled reference population (healthcare workers entirely without patient contact, n=3,671; 9.7% seropositivity). Only 13/379 employees (3.4%) had evidence of a current infection (PCR positivity). Among these, 5 were also seropositive (a sign of past infection or lingering infection after symptoms have resolved) and 3 were positive with only low amounts of virus. The combination of high amounts of virus and no antibodies, a characteristic for pre-symptomatic COVID-19, was thus present only in 5 employees (1.3%). ConclusionsPersonnel providing home service for the elderly appear to be a risk group for SARS-CoV-2 infection. Employees likely to be pre-symptomatic for COVID-19 can be readily identified by screening. Increased attention for protection of employees as well as of the elderly they serve is warranted.

Screening for high amounts of SARS-CoV-2 identifies pre-symptomatic subjects among healthy healthcare workers

BackgroundPre-symptomatic subjects are spreaders of SARS-CoV-2 infection, and strategies that could identify these subjects, particularly in hospital settings, are needed. MethodsWe tested a cohort of 9449 employees at work at the Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the screening results to sick leave records and examined the association between screening results and past or future sick leave using multinomial logistic regression. ResultsWe found that healthcare workers with high amounts of SARS-CoV-2 virus, as indicated by the Cycle threshold (Ct) value in the PCR, had the highest risk for sick leave in the two weeks after testing (OR 11{middle dot}97 (CI 95% 6{middle dot}29-22{middle dot}80)) whereas subjects with low amounts of virus had the highest risk for sick leave in the past three weeks before testing (OR 6{middle dot}31 (4{middle dot}38-9{middle dot}08)). Only 2{middle dot}5% of employees were SARS-CoV-2 positive while 10{middle dot}5% were positive by serology and 1{middle dot}2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR 1{middle dot}06 (95% CI, 0{middle dot}71-1{middle dot}57)), but virus-positive subjects had a 7{middle dot}23 fold (95% CI, 4{middle dot}52-11{middle dot}57)) increased risk for sick leave within two weeks post testing. ConclusionsScreening of asymptomatic healthcare workers for high amounts of SARS-CoV-2 virus using Ct values will identify pre-symptomatic subjects who will develop disease in the next few weeks. Identification of potentially contagious, pre-symptomatic subjects is likely critical for protecting patients and healthcare workers. Main pointHealthy healthcare workers with low amounts of SARS-CoV-2 nucleic acids will previously have had the disease. Presence of a high amount of SARS-CoV-2 nucleic acids predicts future symptomatic disease.

Antibodies to SARS-CoV-2 and risk of future sickness

Background: The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. Method: We analyzed 12928 healthy hospital employees for SARS-CoV-2 antibodies and compared results to participant sick leave records (Clinical trial registration: ClinicalTrials.gov NCT04411576). Results: Subjects with viral serum antibodies were not at excess risk for future sick leave (Odds Ratio (OR): 0.85 (95% Confidence Interval (CI) (0.85 (0.43-1.68)). By contrast, subjects with antibodies had an excess risk for sick leave in the past weeks (OR: 3.34 (2.98-3.74)). Conclusion: Presence of viral antibodies marks past disease and protection against excess risk of future disease.

Estimating COVID-19 contribution to total excess mortality

We compared the total excess mortality per week in relation to the reported Covid-19 related deaths in the Stockholm region (Sweden). Total excess mortality peaked under the weeks of high COVID-19-related mortality, but 25% of these deaths were not recognized as Covid-related. Most of these deaths occurred outside hospitals. Total all-cause mortality in excess to average all-cause mortality during the epidemic peak period may provide a comprehensive picture of the total burden of COVID19-related deaths.

A systematic review of convalescent plasma treatment for COVID19

BackgroundTransfusion of convalescent immune plasma (CP) is commonly used in epidemics. Several articles now describe clinical report data of CP for treatment of SARS-CoV-2-induced COVID-19 disease. MethodsA systematic literature review was conducted using the NCBI curated COVID-19 related open-resource literature database LitCovid to identify studies using CP as treatment for COVID-19 patients. We retrieved and curated all COVID-19 related patient and treatment characteristics from previously reported studies. A Poisson model was developed to evaluate the association between age of the patients, older age being the most common risk factor for COVID-19 mortality, and recovery time since CP treatment using data extracted from the literature. ResultsFrom 18,293 identified COVID-19 related articles, we included ten studies reporting results of CP treatment for COVID-19 from a total of 61 patients. Decreased symptoms of severe COVID-19 and clearance of SARS-CoV-2 RNA were the most direct observations. We found that patients over the age of sixty who received CP treatment for COVID-19 had a significantly prolonged recovery estimated by viral clearance (from 10 to 29 days since first dose of CP) compared to younger patients, who recovered from the infection in less than a week after receiving CP treatment. ConclusionsLimited published results on plasma transfusion treatment for COVID-19 disease with concomitant treatments suggest that CP therapy for COVID-19 is well tolerated and effective. First randomized clinical trial results, however, revealed no improvements in recovery time for elderly patients with severe COVID-19 between standard treatment alone and added with convalescent plasma. Accordingly, we argue that older patients may need a significantly longer time for recovery. Further randomized clinical trial data for COVID-19 with rigorous ethical standards is urgently needed.

HPV-mRNA and HPV-DNA detection in samples taken up to seven years before severe dysplasia of cervix uteri.

Randomized clinical trials using human papillomavirus (HPV) DNA testing have found increased protection against cervical cancer and HPV-based screening is globally recommended for women ≥30 years of age. HPV-mRNA is a promising alternative target for cervical screening tests, but assessing equivalence requires longitudinal evaluation over at least the length of a screening interval. Our aim is to analyze the longitudinal sensitivity of HPV-mRNA and HPV-DNA in cervical samples taken up to 7 years before severe cervical intraepithelial neoplasia or worse (CIN3+). From a population-based cohort of 95,023 women in Sweden, cervical samples were frozen at -80°C between May 2007 and January 2012. Registry linkages identified that 1,204 of these women had CIN3+ 4 months to 7 years after enrolment. Baseline samples were analyzed for HPV-mRNA (Aptima, Hologic) and for HPV-DNA (Cobas 4800, Roche) and results from both tests obtained for 1,172 women. For both women <30 and ≥ 30 years, HPV-mRNA had similar sensitivity for CIN3+ as HPV-DNA (p = 0.0217 and p = 0.0123 in noninferiority testing for at least 90% relative sensitivity, respectively). Among women ≥30 years, the longitudinal sensitivities for CIN3+ occurring 5-7 years later were comparable [76.3% (95% CI: 65.8%-84.3%) and 82.5% (95% CI: 72.6%-89.4%)] as were the longitudinal negative predictive values for absence of CIN3+ [99.97% (95% CI: 99.95-99.98) and 99.98% (95% CI: 99.96-99.99)], for the HPV-mRNA and HPV-DNA test. In conclusion, HPV-mRNA testing has similar longitudinal sensitivity as HPV-DNA, implying that HPV-mRNA testing can safely be used for cervical screening.

Community influences on married men's uptake of HIV testing in eight African countries.

Despite efforts to increase HIV testing in the African region, the proportion of men who report ever having been tested for HIV remains low. Research has focused on individual level determinants of women's testing however little is known about factors associated with men's testing behavior. This analysis investigates community influences on HIV testing among men ages 15-54, using Demographic and Health Survey (DHS) data from Chad, Ghana, Malawi, Nigeria, Tanzania, Uganda, Zambia, and Zimbabwe. Multilevel models were fitted in each country for the outcome of ever receiving an HIV test. After controlling for individual and household level factors, community level factors of demographics, economics, and behavior and knowledge remain significantly associated with HIV testing among men. The results of this analysis highlight the need to recognize the impact of community influences on men's HIV test seeking behavior, and to harness these community factors in the design of programs aimed at encouraging the uptake of HIV testing among men in Africa.