Pre-vaccine Era Research Articles

Outcomes in COVID-19 patients undergoing laparoscopic cholecystectomy/appendectomy in the pre-vaccine era

BackgroundWe hypothesized that COVID-19 positive patients requiring laparoscopic cholecystectomy (lap chole) or appendectomy (lap appy) would have increased inpatient mortality rates compared to all COVID-19 patients. MethodsRetrospective cohort analysis including COVID-19 patients from 1/1/20 to 9/30/20. 82,574 cases identified. Patients excluded if <18 years old or underwent surgery other than lap chole or lap appy. Control groups were patients without surgery (N = 82,145). Exposure groups underwent lap chole (N = 323) or lap appy (N = 106). Primary outcome was inpatient mortality. Secondary outcomes included hospital length of stay (LOS) and complications such as bacterial pneumonia, deep venous thrombosis (DVT), pulmonary embolism (PE), urinary tract infection (UTI), acute myocardial infarction (MI), acute respiratory distress syndrome (ARDS), and respiratory failure (RF). ResultsOverall inpatient mortality rate was 32.8% in COVID-19 patients undergoing lap chole (p-value <0.0001), 2.8 % lap appy (p-value 0.93), and 1.2 % in control group. ARDS complication rate was 11.2 % in lap chole (p-value <0.0001), 1.9 % lap appy (p-value 0.71), and 0.2 % in control. ConclusionCOVID-19 patients during the initial wave of the pandemic who underwent lap chole during hospital admission had significantly higher risk of mortality and ARDS while lap appy did not.

A COVID-19 Overview from the Perspective of the Brazilian Kidney Transplantation Program

The Coronavirus disease 2019 (COVID-19) has significantly affected kidney transplantation activities around the world, thus resulting in a substantial decrease in both deceased and living transplants. This study presents a COVID-19 overview from the perspective of the Brazilian kidney transplant program by comparing its differences or similarities with the situations observed in other countries. During the first year of the pandemic, there was a 40% reduction in the number of kidney transplants worldwide. A similar scenario was observed in Brazil, which has the world’s largest public transplantation program. Beyond its effect on transplant activity, COVID-19 has influenced the outcomes of prevalent kidney transplant recipients (KTRs) because the prolonged use of immunosuppressive drugs and comorbidities increase the susceptibility of such patients to severe disease and death. In the pre-vaccination era, almost two-thirds of KTRs required hospitalization, more than 20% required dialysis, and one-third was admitted to the intensive care unit. In the pre-vaccination period in Brazil, 15% and 21% of KTRs died within 28 and 90 days of COVID-19 diagnosis, respectively. Although high vaccination coverage rates have altered the COVID-19 landscape in many populations, persistently low immunogenicity rates following sequential vaccination shots and the absence of targeted treatments for severe cases continue to classify KTRs as highly vulnerable, thus warranting significant concern.

Increased Risk of Herpes Zoster in Adult Patients with Inflammatory Bowel Disease After SARS-CoV2 Infection: A Propensity-Matched Cohort Study.

There is evidence that SARS-CoV2 infection can increase the risk of herpes zoster (HZ) in the general population. However, the risk in patients with inflammatory bowel disease (IBD) is not known. The TriNetX database was utilized to conduct a retrospective cohort study in patients with IBD after SARS-CoV2 infection and patients without a SARS-CoV2 infection (IBD control cohort). The primary outcome was to evaluate the risk of HZ between the 2 cohorts. One-to-one (1:1) propensity score matching was performed for demographic parameters, HZ risk factors and IBD medications between the 2 cohorts. Adjusted odds ratio (aOR) with 95% confidence interval (CI) were calculated. After propensity score matching, patients with IBD with a SARS-CoV2 infection were at an increased risk for HZ (aOR, 2.16; 95% CI, 1.53-3.04) compared with IBD control cohort in the pre-COVID-19 vaccine era. There was no difference in the risk (aOR, 0.87; 95% CI, 0.44-1.75) of a composite outcome of HZ complications (hospitalization, post-herpetic neuralgia, and neurologic complications) between the 2 cohorts. The IBD SARS-CoV2 cohort was also at an increased risk for HZ (aOR, 3.04; 95% CI, 1.48-6.24) compared with IBD control cohort in the postvaccine era. However, the risk of HZ in the postvaccine era was decreased (aOR, 0.45; 95% CI, 0.27-0.76) compared with IBD SARS-CoV2 cohort in the prevaccine era. Our study showed that SARS-CoV2 infection is associated with an increased risk of HZ in patients with IBD.

Were cancer patients worse off than the general population during the COVID-19 pandemic? A population-based studyfrom Norway, Denmark and Iceland during the pre-vaccination era.

In a population-based setting, we investigated the risks of testing positive for SARS-CoV-2 and developing severe COVID-19 outcomes among cancer patients compared with the general population. In nationwide cohorts, we identified all individuals in Norway, Denmark and Iceland who tested positive for SARS-CoV-2 or had a severe COVID-19 outcome (hospitalisation, intensive care, and death) from March until December 2020, using data from national health registries. We estimated standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) comparing cancer patients with the general population. During the first wave of the pandemic, cancer patients in Norway and Denmark had higher risks of testing SARS-CoV-2 positive compared to the general population. Throughout 2020, recently treated cancer patients were more likely to test SARS-CoV-2 positive. In Iceland, cancer patients experienced no increased risk of testing positive. The risk of COVID-19-related hospitalisation was higher among cancer patients diagnosed within one year of hospitalisation (Norway: SIR=2.43, 95% CI 1.89-3.09; Denmark: 2.23, 1.96-2.54) and within five years (Norway: 1.58, 1.35-1.83; Denmark: 1.54, 1.42-1.66). Risks were higher in recently treated cancer patients and in those diagnosed with haematologic malignancies, colorectal or lung cancer. Risks of COVID-19-related intensive care and death were higher among cancer patients. Cancer patients were at increased risk of testing positive for SARS-CoV-2 during the first pandemic wave when testing availability was limited, while relative risks of severe COVID-19 outcomes remained increased in cancer patients throughout 2020. Recent cancer treatment and haematologic malignancy were the strongest risk factors. Nordic Cancer Union.

Distribution of HPV Types in Tumor Tissue from Non-Vaccinated Women with Cervical Cancer in Norway

Background: Understanding the distribution of HPV types in cervical cancer cases is crucial for evaluating the effectiveness of HPV screening and vaccination in reducing cervical cancer burden. This study aimed to assess genotype prevalence in the pre-vaccine era among 178 cervical cancer cases detected during a 20-year screening period in Northern Norway and compare the potential efficacy of HPV vaccines in preventing cervical cancer. Methods: A total of 181 formalin-fixed paraffin-embedded (FFPE) tissue samples from non-vaccinated women diagnosed with cervical cancer between 1995 and 2015 in Troms and Finnmark, Norway, were analyzed using a 45-type HPV DNA test. The results were compared to a 7-type HPV mRNA test targeting oncogenic types included in the nonavalent HPV vaccine. Results: Invalid HPV test results were observed in 1.7% (3/181) of the samples and were subsequently excluded from further analysis. Among the remaining cases, 92.7% (165/178) tested positive for HPV using any test combination. HPV DNA was detected in 159 cases (89.3%), while HPV mRNA was detected in 149 cases (83.7%). The most prevalent HPV types were 16 and 18, responsible for 70.8% of the cases, with the nonavalent vaccine types accounting for 86.6% of cases. HPV 35 was identified in eight cases (4.5%). Conclusion: The bivalent/quadrivalent HPV vaccines have the potential to prevent 76.4% (126/165) of HPV-positive cervical cancer cases, while the nonavalent vaccine could prevent 93.3% (154/165) of cases. Tailoring screening strategies to target HPV types with the highest oncogenic potential may improve cervical cancer detection and enable targeted interventions for high-risk individuals. The use of a 7-type HPV mRNA test holds promise as an advantageous approach.

Trends in severe outcomes in SARS-CoV-2-positive hospitalized patients with rheumatic diseases: a monocentric observational and case-control study in northern Italy.

Rheumatic disease patients are at greater risk of infection due to their disease, comorbidities, and immunosuppressive therapy. COVID-19 outcomes in this patient setting appeared to be similar to those of the general population. However, data on this topic were mainly related to small studies on a limited number of patients. Consequently, to date, this field remains poorly explored, particularly in the pre-vaccine era. This monocentric study aimed to describe the intrahospital mortality in rheumatic patients with SARS-CoV-2 consecutively hospitalized from 21 February to 31 December 2020, before anti-SARS-CoV-2 vaccine administration spread, compared with non-rheumatic patients. Of 2491 included patients, 65 [3%, median (interquartile range) age 75 (64.76-82.239 years, 65% women] were suffering from rheumatic diseases. A total of 20 deaths were reported [case fatality rate 31%, 95% confidence interval (CI): 19-42] compared with 433 deaths (19%, 95% CI: 17-20) in patients without rheumatic diseases (p=0.024). However, the rheumatic disease was not associated with a significant increase in univariate mortality hazards (hazard ratio 1.374, 95% CI: 0.876-2.154), and after adjustment (hazard ratio 1.199, 95% CI: 0.759-1.894) by age, sex and Charlson comorbidity index. The incidence of intensive care unit admission, death, and discharge in the case-control study was comparable between rheumatic and non-rheumatic patients. The presence of rheumatic diseases in SARS-CoV-2-hospitalized patients did not represent an independent risk factor for severe disease or mortality.

Does tourism affect the long term course of COVID-19 pandemic in a country of destination? Evidence from a popular Greek island in 2020 where control measures were implemented.

Greece opened its points of entry on July 1, 2020, with specific guidelines for travellers arriving by sea, air or land. The aim of this article is to examine the effect of tourism on the long term course of the Coronavirus Disease 2019 (COVID-19) pandemic during the pre-vaccination era (June to December 2020) on the popular Greek island of Crete. To achieve this, a cross-sectional serosurvey, repeated at monthly intervals, was conducted to compare the seroprevalence in Crete with seroprevalence in the mainland of Greece. Crete welcomed nearly 2,000,000 travellers during the 2020 summer season. Left-over serum samples were collected and obtained from public and private laboratories located in Greece, including the island of Crete. These samples were tested for the presence of anti-SARS-CoV-2 IgG antibodies. A total of 55,938 samples were collected, 3,785 of which originated from Crete. In Crete, the seroprevalence ranged between 0% (June 2020) and 2.58% (December 2020), while the corresponding seroprevalence in Greece was 0.19% and 10.75%, respectively. We identified 4.16 times lower seropositivity in Crete (2.58%) in comparison with the mainland of Greece (10.75%) during December 2020. Moreover, the monthly infection fatality rate (IFR) in Crete was calculated at 0.09%, compared with 0.21% in mainland Greece for December 2020. The island of Crete presented more than four times lower seroprevalence than the mainland of Greece, despite being a highly attractive tourist destination. This evidence supports the idea that tourism may not have affected the long term course of the COVID-19 pandemic in Greece. However, due to contradicting results from previous studies, further investigation is needed.

The Association between Varicella Vaccination and Herpes Zoster in Children: A Semi-National Retrospective Study.

Varicella vaccination in children has been performed worldwide in recent years. Despite established effectiveness, many countries still do not routinely vaccinate children against varicella, probably due to concerns about complications, such as herpes zoster infection. We aimed to compare the herpes zoster incidence in children before and after implementing the mandatory varicella vaccine in Israel in 2008. As a secondary aim, we characterized several parameters, including age, sex, and ethnic sector among herpes zoster cases, and we evaluated the complication rate to identify data relevant to the immunization status of the pediatric population. A retrospective study was conducted between 2000 and 2021, including patients aged 0-18 years old in a large cohort in southern Israel. A time series analysis and complication rates evaluations were performed in the pre- and post-vaccination eras. A total of 109.24 herpes zoster cases per 100,000 population per year were diagnosed between 2000 and 2007 (pre-vaccination era), compared to 354.71 herpes zoster cases per 100,000 population per year diagnosed between 2008 and 2021 (post-vaccination era) (p < 0.001). No change in the complication rate was documented. Thus, we concluded that there is an association between the varicella vaccine implementation program and the increase in the rate of herpes-zoster occurrence without a concurrent negative contribution to herpes zoster-related morbidity.

COVID-19 burden differed by city districts and ethnicities during the pre-vaccination era in Amsterdam, the Netherlands.

During the first wave of COVID-19 in Amsterdam, the Netherlands, a disproportional number of COVID-19 hospitalizations occurred in individuals with an ethnic minority background and in individuals living in city districts with a lower socioeconomic status (SES). In this study, we assessed whether these disparities continued throughout the second wave, when SARS-CoV-2 testing was available to anyone with symptoms but prior to the availability of COVID-19 vaccination. Surveillance data on all notified SARS-CoV-2 cases in Amsterdam between 15 June 2020 and 20 January 2021 were matched to municipal registration data to obtain the migration background of cases. Crude and directly age- and sex-standardized rates (DSR) of confirmed cases, hospitalizations, and deaths per 100,000 population were calculated overall, and by city districts, and migration backgrounds. Rate differences (RD) and rate ratios (RR) were calculated to compare DSR between city districts and migration backgrounds. We used multivariable Poisson regression to assess the association of city districts, migration backgrounds, age, and sex with rates of hospitalization. A total of 53,584 SARS-CoV-2 cases (median age 35 years [IQR = 25-74]) were notified, of whom 1,113 (2.1%) were hospitalized and 297 (0.6%) deceased. DSR of notified infections, hospitalization, and deaths per 100,000 population were higher in lower SES peripheral city districts (South-East/North/New-West) than higher SES central districts (Central/West/South/East), with almost a 2-fold higher hospitalization DSR in peripheral compared to central districts (RR = 1.86, 95%CI = 1.74-1.97). Individuals with a non-European migration background also had a higher COVID-19 burden, particularly with respect to hospitalization rates, with a 4.5-fold higher DSR for individuals with a non-European background compared to ethnic-Dutch (RR 4.51, 95%CI = 4.37-4.65). City districts, migration backgrounds, male gender, and older age were independently associated with COVID-19 hospitalization rates. Individuals with a non-European background and individuals living in city districts with lower SES continued to independently have the highest COVID-19 burden in the second wave of COVID-19 in Amsterdam, the Netherlands.

Public health impact and return on investment of Belgium's pediatric immunization program.

We evaluated the public health impact and return on investment of Belgium's pediatric immunization program (PIP) from both healthcare-sector and societal perspectives. We developed a decision analytic model for 6 vaccines routinely administered in Belgium for children aged 0-10 years: DTaP-IPV-HepB-Hib, DTaP-IPV, MMR, PCV, rotavirus, and meningococcal type C. We used separate decision trees to model each of the 11 vaccine-preventable pathogens: diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, Streptococcus pneumoniae, rotavirus, and meningococcal type C; hepatitis B was excluded because of surveillance limitations. The 2018 birth cohort was followed over its lifetime. The model projected and compared health outcomes and costs with and without immunization (based on vaccine-era and pre-vaccine era disease incidence estimates, respectively), assuming that observed reductions in disease incidence were fully attributable to vaccination. For the societal perspective, the model included productivity loss costs associated with immunization and disease in addition to direct medical costs. The model estimated discounted cases averted, disease-related deaths averted, life-years gained, quality-adjusted life-years gained, costs (2020 euros), and an overall benefit-cost ratio. Scenario analyses considered alternate assumptions for key model inputs. Across all 11 pathogens, we estimated that the PIP prevented 226,000 cases of infections and 200 deaths, as well as the loss of 7,000 life-years and 8,000 quality-adjusted life-years over the lifetime of a birth cohort of 118,000 children. The PIP was associated with discounted vaccination costs of €91 million from the healthcare-sector perspective and €122 million from the societal perspective. However, vaccination costs were more than fully offset by disease-related costs averted, with the latter amounting to a discounted €126 million and €390 million from the healthcare-sector and societal perspectives, respectively. As a result, pediatric immunization was associated with overall discounted savings of €35 million and €268 million from the healthcare-sector and societal perspectives, respectively; every €1 invested in childhood immunization resulted in approximately €1.4 in disease-related cost savings to the health system and €3.2 in cost savings from a societal perspective for Belgium's PIP. Estimates of the value of the PIP were most sensitive to changes in input assumptions for disease incidence, productivity losses due to disease-related mortality, and direct medical disease costs. Belgium's PIP, which previously had not been systematically assessed, provides large-scale prevention of disease-related morbidity and premature mortality, and is associated with net savings to health system and society. Continued investment in the PIP is warranted to sustain its positive public health and financial impact.

One Big Cry

One Big Cry

Assessing Convalescent Plasma Efficacy in Moderate COVID-19 Hospitalizations: A Bicentric Retrospective Study

COVID-19 claimed millions of lives, mainly in the pre-vaccine era. Preliminary studies showed promising efficacy of convalescent plasma against SARS-CoV-2 (CP). To evaluate the efficacy of CP in patients hospitalized for COVID-19 with moderate severity. Retrospective, bicentric study including adults hospitalized for moderate (non-critical) COVID-19 who required oxygen therapy. CP donated by survivors of mild cases (600 cc) were searched for IgG anti-SARS-CoV-2. Its impact on mortality, hospital stay (days), and need for mechanical ventilation (IMV) was evaluated. Of the 119 patients included, 58% were men (median age 60 years), 88% had comorbidity, and 43% had a high-risk CALL score. Forty-three patients (36%) received CP, only 15 (12.6%) early (< 7 days). Twenty-two patients had to be transferred to the intensive care unit; 18 received IMV, and 15 died (12.6%). The use of CP was not associated with changes in mortality (p = 0.16), need for IMV (p = 0.79), or hospital stay (p = 0.24). Its early administration (< 7 days of symptoms) did not show a significant association either. The presence of heart disease and subsequently requiring IMV were independent factors of mortality. The use of CP in patients hospitalized for moderately severe COVID-19 was not associated with lower mortality, hospital stay, or the need for IMV.

Mortality predictors in hospitalised COVID-19 patients and the role of anti-SARS-CoV-2 IgG antibodies and remdesivir.

In a pre-vaccination era serologic tests may be used to evaluate the seroprevalence and efficacy of containment strategies applied to the community. Subsequently, SARS-CoV-2 vaccination has successfully reduced hospitalization and admission to intensive care. The role of antiviral treatment for COVID-19 remains debated. We investigated the effect of SARS-CoV-2 IgG Spike (S) antibody responses in hospitalized patients on 30-day mortality. Finally, we assessed whether other predictive factors affected mortality after 30 days. Observational study on COVID-19 patients admitted from October 1, 2021, to January 30, 2022. 520 patients were studied; 108 died at the 30-day follow-up (21%). A borderline significance for mortality was observed in favour of the high antibody titer group (24% vs 17%, p=0.05). From the univariate Cox regression analysis, a high IgG-S titer was significantly correlated to lower 30-day mortality (p=0.04, HR: 0.7; 95%CI: 0.44-0.98). The administration of remdesivir (p=0.01) and the age <65 years (p=2.3e-05) were found to be protective for the considered outcome (respectively, HR: 0.5, 95%CI: 0.34-0.86, and HR: 0.1, 95%CI: 0.04-0.30). S-antibodies and remdesivir could play a protecting role in increasing the survival of hospitalized COVID-19 patients who are not suffering from a critical disease. Advanced age is a risk factor for poor outcomes among infected people.

Antibody Response to the SARS-CoV-2 Vaccine and COVID-19 Vulnerability during the Omicron Pandemic in Patients with CLL: Two-Year Follow-Up of a Multicenter Study.

High morbidity and mortality due to COVID-19 were described in the pre-vaccination era in patients with chronic lymphocytic leukemia (CLL). To evaluate COVID-19 morbidity after the SARS-CoV-2 vaccine, we carried out a prospective study in 200 CLL patients. The median age of patients was 70 years; 35% showed IgG levels ≤ 550 mg/dL, 61% unmutated IGHV, and 34% showed TP53 disruption. Most patients, 83.5%, were previously treated, including 36% with ibrutinib and 37.5% with venetoclax. The serologic response rates to the second and third dose of the vaccine were 39% and 53%, respectively. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19, 36.5% during the Omicron pandemic, and 10% had subsequent COVID-19 events. Severe COVID-19 requiring hospitalization was recorded in 26% of patients, and 4% died. Significant and independent factors associated with the response to the vaccine and vulnerability to COVID-19 were age (OR: 0.93; HR: 0.97) and less than 18 months between the start of targeted agents and vaccine (OR: 0.17; HR: 0.31). TP53 mutation and ≥two prior treatments also emerged as significant and independent factors associated with an increased risk of developing COVID-19 (HR: 1.85; HR: 2.08). No statistical difference in COVID-19 morbidity was found in patients with or without antibody response to the vaccine (47.5% vs. 52.5%; p = 0.21). Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in CLL patients.

Association of endometriosis with genital human papillomavirus infection in US women: a national population-based study

The prevalence of genital human papillomavirus (HPV) in women with endometriosis has never been reported in a national representative survey. We aimed to investigate the association of endometriosis with the prevalence of HPV. We analyzed the data on 1768 women (representing 43,824,157 women) in the United States aged 20–54 years from the National Health and Nutrition Examination Survey in the prevaccination era (2003–2006). The diagnosis of endometriosis was based on a self-report. The prevalence of any HPV in women with endometriosis did not differ from that in women without endometriosis after controlling for potential confounders such as age, ethnicity, family income, marital status, and the number of deliveries (adjusted prevalence ratio (aPR) 0.84, 95% confidence interval (CI) 0.61–1.15). No significant association was found between the prevalence of high-risk HPV and the diagnosis of endometriosis (aPR 0.71, 95% CI 0.44–1.14). If the participants were not covered by health insurance, the prevalence of any HPV infection in women with endometriosis was higher than in those without endometriosis (aPR 1.44, 95% CI 0.94–2.20). In contrast, in a subgroup who had health insurance, a lower prevalence of any HPV infection was observed in women with endometriosis (aPR 0.71, 95% CI 0.50–1.03), and P for interaction was statistically significant (P = 0.01). There was no association between endometriosis and HPV infection in this study of HPV vaccine-naïve women of reproductive age. The association was not different by the type of HPV. However, access to healthcare may modify the association between endometriosis and HPV infection.

Differences in clinical characteristics and outcomes between COVID-19 and influenza in critically ill adult patients: A national database study

Prior to the coronavirus disease 2019 (COVID-19) pandemic, influenza was the most frequent cause of viral respiratory pneumonia requiring intensive care unit (ICU) admission. Few studies have compared the characteristics and outcomes of critically ill patients with COVID-19 and influenza. This was a French nationwide study comparing COVID-19 (March 1, 2020-June 30, 2021) and influenza patients (January 1, 2014-December 31, 2019) admitted to an ICU during pre-vaccination era. Primary outcome was in-hospital death. Secondary outcome was need for mechanical ventilation. 105,979 COVID-19 patients were compared to 18,763 influenza patients. Critically ill patients with COVID-19 were more likely to be men with more comorbidities. Patients with influenza required more invasive mechanical ventilation (47 vs. 34%, p<0·001), vasopressors (40% vs. 27, p<0·001) and renal-replacement therapy (22 vs. 7%, p<0·001). Hospital mortality was 25 and 21% (p<0·001) in patients with COVID-19 and influenza, respectively. In the subgroup of patients receiving invasive mechanical ventilation, ICU length of stay was significantly longer in patients with COVID-19 (18 [10-32] vs. 15 [8-26] days, p<0·001). Adjusting for age, gender, comorbidities, and modified SAPS II score, in-hospital death was higher in COVID-19 patients (adjusted sub-distribution hazard ratio [aSHR]=1.69; 95%CI=1.63-1.75) compared with influenza patients. COVID-19 was also associated with less invasive mechanical ventilation (aSHR=0.87; 95%CI=0.85-0.89) and a higher likelihood of death without invasive mechanical ventilation (aSHR=2.40; 95%CI=2.24-2.57). Despite younger age and lower SAPS II score, critically ill COVID-19 patients had a longer hospital stay and higher mortality than patients with influenza.

P63 BREAKTHROUGH COVID-19 IN FULL VACCINATED PATIENTS WITH MULTIPLE MYELOMA: A SINGLE CENTER EXPERIENCE OF 54 PATIENTS

COVID-19-related mortality in the onco-hematological setting is higher than in general population and patients with multiple myeloma (MM) are reported to be particularly vulnerable to SARS-CoV-2 infection, due to compromised humoral and cellular immunity (related to disease itself) and to anti-tumor treatments. Thus, along with general measures, vaccines against SARS-CoV-2 have become, from their approval, the most important strategy to prevent poor outcome from COVID-19 in MM patients. However, limited data have been so far published about epidemiology and outcome of breakthrough COVID-19 in MM patients after three anti-SARS-CoV-2 vaccine doses. We performed a retrospective analysis of 54 consecutive patients with active MM who experienced SARS-CoV-2 infection between December, 2021, and December, 2022 at our Institution (Table 1). Among them, four cases of “reinfection” were documented. All patients had received three doses of anti-SARS-CoV2 vaccines (mostly mRNA) and 6 of them had also received a fourth, “second booster” dose. SARS-CoV-2 infections were diagnosed by RT-PCR or by antigen rapid test on nasopharyngeal swabs. Data about sex, age, ongoing treatment, symptoms, hospitalization, mortality, and additional use of antiviral drugs or monoclonal antibodies for the treatment of COVID-19 were collected. The median age of the whole group was 65 years (IQR: 60-76; range: 39-84), with male preponderance (59.3%). Half of the patients (27) had at least one underlying comorbidity, with chronic cardiopathy (i.e., hypertension, atrial fibrillation) being the most reported. The most frequent isotype was IgG, followed by IgA, light chain and non-secreting subtype. Median number of days between the last dose of vaccine and infection was 136.5 (IQR: 89-199.2; range: 11-381). About disease status at SARS-CoV-2 breakthrough infection, 27 cases (50%) were newly diagnosed/first line MM, 20 (37%) were first relapses, 7 (13%) were further relapsed MM. Forty-eight patients (88.9%) were under treatments including dexamethasone (64.8%), proteosome inhibitors (25.9%), IMiDs (75.9%), anti-CD38 monoclonal antibodies (44.4%) or other therapies (7.4%). Six patients (11.1%) in complete response, three of whom after autologous transplantation and one after CAR-T treatment, were in follow-up, without active therapy. Infection was symptomatic in 35 patients (64.8%) and the most common symptoms were fever, cough, sore throat and runny nose. Overall, 4 patients (7.4%) were hospitalized: among them, 1 (1.8%) was admitted to an intensive care unit (ICU) due to respiratory distress. Fourteen patients (25.9%) received specific anti-SARS-CoV-2 treatment: 7molnupivar, 5 PF-07321332/ritonavir, 1 PF-07321332/ritonavir + sotrovimab, 1 sotrovimab. After a median follow-up of 258 days (IQR: 181-294; range: 43-356), 3 patients (5.6%) had died and no patient reported long-lasting symptoms. Our data indicate that SARS-CoV-2 infection remains frequent even in “triple vaccinated” MM patients, but also that the clinical outcome of COVID-19 appears to be significantly improved by a “booster” dose of vaccine with respect to pre-vaccination era in this high risk population exposed to novel Omicron variants. The role of new antiviral agents and monoclonal antibodies, currently used to reduce the risk of progression of COVID-19 to severe disease, warrants to be further investigated in larger series. Table 1 - Characteristics of 54 full vaccinated MM patients with SARS-CoV-2 infection Age, years Median (IQR)Range 65 (60-76)39-84 Sex, n. (%)MaleFemale 32 (59.3)22 (40.7) Comorbidities, n. (%)012≥3 27 (50)16 (29.7)5 (9.2)6 (11.1) MM subtype, n. (%)IgGIgALight chainNon-secreting 33 (61.1)12 (22.2)7 (13)2 (3.7) Days from last vaccine dose to SARS-CoV-2 infection Median (IQR)Range 136.5 (89-199.2)11-381 Disease status, n. (%)Newly diagnosed/First line1st RelapseRelapse-Refractory 27 (50)20 (37)7 (13) Current MM treatment, n. (%) Dexamethasone Contains Proteosome inhibitor Bortezomib Carfilzomib Ixazomib Contains IMiD (including maintenance therapy) Thalidomide Lenalidomide Pomalidomide Contains CD38 mAb Daratumumab Isatuximab Contains other Elotuzumab, Belantamab Mafodotin Melphalan No therapies 48 (88.9)35 (64.8)14 (25.9)93241 (75.9)632324 (44.4)2224 (7.4)211 6 (11.1) COVID-19 outcome, n. (%)Presence of symptomsHospitalizationHospitalization in ICUDeath to COVID-19 35 (64.8)4 (7.4)1 (1.8)3 (5.6) COVID-19 symptoms, n. (%)FeverCoughSore throatRunny noseFatigueDiarrhea 28 (80)14 (40)11 (31.4)11 (31.4)6 (11.1)3 (8.6) Treatment, n. (%)MolnupiravirPF-07321332/RitonavirPF-07321332/Ritonavir + SotrovimabSotrovimabNone 7 (13)5 (9.3)1 (1.8)1 (1.8)40 (74.1)

Persistent Immunity against SARS-CoV-2 in Individuals with Oncohematological Diseases Who Underwent Autologous or Allogeneic Stem Cell Transplantation after Vaccination

The high morbimortality due to SARS-CoV-2 infection in oncohematological diseases (OHD) and hematopoietic stem cell transplant (HSCT) recipients in the pre-vaccine era has made vaccination a priority in this group. After HSCT, the immune responses against common vaccines such as tetanus, varicella, rubella, and polio may be lost. However, the loss of immunity developed by COVID-19 vaccination after HSCT has not been completely defined. In this study, both humoral and cellular immunity against SARS-CoV-2 were analyzed in 29 individuals with OHD who were vaccinated before receiving allogeneic (n = 11) or autologous (n = 18) HSCT. All participants had low but protective levels of neutralizing IgGs against SARS-CoV-2 after HSCT despite B-cell lymphopenia and immaturity. Although antibody-dependent cellular cytotoxicity was impaired, direct cellular cytotoxicity was similar to healthy donors in participants with autologous-HSCT, in contrast to individuals with allogeneic-HSCT, which severely deteriorated. No significant changes were observed in the immune response before and after HSCT. During follow-up, all reported post-HSCT SARS-CoV-2 infections were mild. This data emphasizes that COVID-19 vaccination is effective, necessary, and safe for individuals with OHD and also supports the persistence of some degree of immune protection after HSCT, at least in the short term, when patients cannot yet be revaccinated.

Care Workers and Managers’ Experiences of Implementing Infection Control Guidance in an Epidemic Context: A Qualitative Study in the South East of England, during the COVID-19 Prevaccination Era

The national response to COVID-19 has had a severe impact on adult social care settings, with high mortality amongst people receiving and providing care in England. Care workers had to rapidly adapt to new infection control measures to protect themselves, their colleagues, and the people receiving care. Infection control in residential and domiciliary care is always complex, but COVID-19 infection control measures impacted exceptionally on care workers’ working and everyday lives. We undertook qualitative interviews with care workers and managers (n = 10) in residential and domiciliary care for older people in the Southeast England during the first wave of the pandemic to understand their experiences, solutions, and concerns to implement guidance in practice. Data were analysed using framework analysis, and the following eight themes were identified: (1) Increasing visibility and support for the sector; (2) the impact of negative messaging about the sector; (3) feelings of isolation; (4) accessibility and usability of guidance; (5) social care staff as agents in producing and sharing good practice; (6) managing expectations and the impact of conflicting messages in the media; (7) improving communication with hospitals; and (8) problems in the early pandemic. The findings reveal widespread concerns for the marginalisation of the sector in the policy response and the inadequacy of infection control guidance. Guidance would benefit from a better understanding of domiciliary and residential care settings. This might involve the following steps: (a) coproduction of guidance with adult social care stakeholders, including those in direct-care roles and (b) a shift away from a clinical model of infection control towards a more flexible approach that attends to the inherent variability of care settings.

Active prospective national surveillance for congenital and neonatal varicella in Australia shows potential prevention opportunities.

To compare the incidence and outcomes of congenital and neonatal varicella in Australia in the pre-vaccination (1995-1997) and post-vaccination era (after 2005 to November 2020), active prospective national surveillance for congenital varicella syndrome (CVS) and neonatal varicella infection (NVI) was conducted through the Australian Paediatric Surveillance Unit (APSU). Compared with 1995-1997, there was a 91.5% reduction in the incidence of CVS and a 91.3% reduction in the incidence of NVI in 2009-2020. However, almost half of the mothers in 2009-2020 were born overseas and came from countries without a vaccination program. Although there has been a substantial and sustained decrease in the reported incidence of CVS and NVI in Australia since 2006, congenital and neonatal varicella infections persist. Thus, there is an opportunity for targeted screening of varicella in young migrant, asylum seeker and refugee women at risk of varicella infection and prioritisation for vaccination to prevent CVS and NVI.