SARS CoV-2 virus in cancer patients: a new unknown in an unsolved equation.

INTRODUCTION: Cancer patients are more susceptible to infections and infection can be more severe than in patients without cancer diagnosis. We conducted this retrospective study in patients admitted for SARS-CoV-2 infection in order to find differences in inflammatory markers and mortality in cancer patients compared to others. METHODS: We reviewed the electronic records of patients admitted for SARS-CoV-2 infection confirmed by PCR from March to September 2020. Data on socio-demographics, comorbidities, inflammatory makers and cancer-related features were analysed. RESULTS: 2,772 patients were admitted for SARS-CoV-2, to the Hospital Universitario Ramón y Cajal in Madrid during this period. Of these, 2597 (91%) had no history of neoplastic disease, 164 (5.9%) patients had a prior history of cancer but were not undergoing oncological treatment at the time of infection, and 81 (2.9%) were in active treatment. Mortality in patients without a history of cancer was 19.5%, 28.6% for patients with a prior history of cancer and 34% in patients with active cancer treatment. Patients in active oncology treatment with the highest mortality rate, were those diagnosed with lung cancer (OR 5.6 95% CI 2.2-14.1). In the multivariate study active oncological treatment (OR 2.259 95% IC 1.35-3.77) and chemotherapy treatment (OR 3.624 95% IC 1.17-11.17), were statistically significant factors for the risk of death for the whole group and for the group with active oncological treatment, respectively. CONCLUSION: Cancer patients on active systemic treatment have an increased risk of mortality after SARS-CoV-2 infection, especially with lung cancer or chemotherapy treatment.

The Negative Impact of COVID-19 in HCV, HIV, and HPV Surveillance Programs During the Different Pandemic Waves

Background The coronavirus disease 2019 (COVID-19) pandemic has been a worldwide stress test for health systems. 2 years have elapsed since the description of the first cases of pneumonia of unknown origin. This study quantifies the impact of COVID-19 in the screening program of chronic viral infections such as human papillomavirus (HPV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) along the six different pandemic waves in our population. Each wave had particular epidemiological, biological, or clinical patterns. Methods We analyzed the number of samples for screening of these viruses from March 2020 to February 2022, the new infections detected in the pandemic period compared to the previous year, the time elapsed between diagnosis and linking to treatment and follow-up of patients, and the percentage of late HIV diagnosis. Moreover, we used the origin of the samples as a marker for quantifying the restoration of activity in primary care. Results During the first pandemic year, the number of samples received was reduced by 26.7, 22.6, and 22.5% for molecular detection of HPV or serological HCV and HIV status respectively. The highest decrease was observed during the first wave with 70, 40, and 26.7% for HPV, HCV, and HIV. As expected, new diagnoses also decreased by 35.4, 58.2, and 40.5% for HPV, HCV, and HIV respectively during the first year of the pandemic. In the second year of the pandemic, the number of samples remained below pre-pandemic period levels for HCV (−3.6%) and HIV (−9.3%) but was slightly higher for HPV (8.0%). The new diagnoses in the second year of the pandemic were −16.1, −46.8, and −18.6% for HPV, HCV, and HIV respectively. Conclusions Undoubtedly, an important number of new HPV, HCV, and HIV infections were lost during the COVID-19 pandemic, and surveillance programs were disrupted as a consequence of collapse of the health system. It is a priority to reinforce these surveillance programs as soon as possible in order to detect undiagnosed cases before the associated morbidity-mortality increases. New pandemic waves could increase the risk of reversing the achievements made over the last few decades.

RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies.

The exact role of viral replication in patients with severe COVID-19 has not been extensively studied, and it has only been possible to demonstrate the presence of replicative virus for more than 3 months in a few cases using different techniques. Our objective was to study the presence of RNA SARS-CoV-2 in autopsy samples of patients who died from COVID-19 long after the onset of symptoms. Secondary superimposed pulmonary infections present in these patients were also studied. We present an autopsy series of 27 COVID-19 patients with long disease duration, where pulmonary and extrapulmonary samples were obtained. In addition to histopathological analysis, viral genomic RNA (gRNA) and viral subgenomic RNA (sgRNA) were detected using RT-PCR and in situ hybridization, and viral protein was detected using immunohistochemistry. This series includes 26 adults with a median duration of 39 days from onset of symptoms to death (ranging 9-108 days), 92% of them subjected to immunomodulatory therapy, and an infant patient. We detected gRNA in the lung of all but one patient, including those with longer disease duration. SgRNA was detected in 11 out of 17 patients (64.7%) with illness duration up to 6 weeks and in 3 out of 9 patients (33.3%) with more than 6 weeks of disease progression. Viral protein was detected using immunohistochemistry and viral mRNA was detected using in situ hybridization in 3 out of 4 adult patients with illness duration of <2 weeks, but in none of the 23 adult patients with an illness duration of >2 weeks. A remarkable result was the detection of viral protein, gRNA and sgRNA in the lung cells of the pediatric patient after 95 days of illness. Additional pulmonary infections included: 9 acute bronchopneumonia, 2 aspergillosis, 2 cytomegalovirus, and 1 BK virus infection. These results suggest that in severe COVID-19, SARS-CoV-2 could persist for longer periods than expected, especially in immunocompromised populations, contributing to the persistence of chronic lung lesions. Additional infections contribute to the fatal course of the disease.

Severe Acute Respiratory Syndrome Coronavirus 2 Spreads to Lymph Nodes and Strongly Expands CD4+ Effector Memory RA Cells in a Patient With Mild Coronavirus Disease 2019.

A woman with mild coronavirus disease 2019 developed cervical adenopathy, being diagnosed of Epstein-Barr virus infectious mononucleosis. We performed fine needle aspiration, and demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in lymph nodes even in mild disease along with a strong expansion of terminally differentiated effector memory CD4+ T cells, a cell population that is practically absent in lymph nodes.

Emergence and Spread of B.1.1.7 Lineage in Primary Care and Clinical Impact in the Morbi-Mortality among Hospitalized Patients in Madrid, Spain.

In December 2020, UK authorities warned of the rapid spread of a new SARS-CoV-2 variant, belonging to the B.1.1.7 lineage, known as the Alpha variant. This variant is characterized by 17 mutations and 3 deletions. The deletion 69-70 in the spike protein can be detected by commercial platforms, allowing its real-time spread to be known. From the last days of December 2020 and over 4 months, all respiratory samples with a positive result for SARS-CoV-2 from patients treated in primary care and the emergency department were screened to detect this variant based on the strategy S gene target failure (SGTF). The first cases were detected during week 53 (2020) and reached >90% of all cases during weeks 15-16 (2021). During this period, the B.1.1.7/SGTF variant spread at a rapid and constant replacement rate of around 30-36%. The probability of intensive care unit admission was twice higher among patients infected by the B.1.1.7/SGTF variant, but there were no differences in death rate. During the peak of the third pandemic wave, this variant was not the most prevalent, and it became dominant when this wave was declining. Our results confirm that the B.1.1.7/SGTF variant displaced other SARS-CoV-2 variants in our healthcare area in 4 months. This displacement has led to an increase in the burden of disease.

The silent epidemic of lymphogranuloma venereum inside the COVID-19 pandemic in Madrid, Spain, March 2020 to February 2021.

Despite social distancing measures implemented in Madrid to prevent the propagation of SARS-CoV-2, a significant increase (57.1%; 28.5 to 38.5 cases/month) in cases of lymphogranuloma venereum was detected during the COVID-19 pandemic. This unusual scenario might have accelerated a shift in Chlamydia trachomatis (CT) epidemiology towards a higher proportion of L genotypes compared with non-L genotypes in CT-positive samples. Our data underscore the importance of surveillance of sexually transmitted infections during the pandemic, in particular among vulnerable populations.

Genomic Epidemiology of SARS-CoV-2 in Madrid, Spain, during the First Wave of the Pandemic: Fast Spread and Early Dominance by D614G Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Madrid, Spain, on 25 February 2020. It increased in frequency very fast and by the end of May more than 70,000 cases had been confirmed by reverse transcription-polymerase chain reaction (RT-PCR). To study the lineages and the diversity of the viral population during this first epidemic wave in Madrid we sequenced 224 SARS-CoV-2 viral genomes collected from three hospitals from February to May 2020. All the known major lineages were found in this set of samples, though B.1 and B.1.5 were the most frequent ones, accounting for more than 60% of the sequences. In parallel with the B lineages and sublineages, the D614G mutation in the Spike protein sequence was detected soon after the detection of the first coronavirus disease 19 (COVID-19) case in Madrid and in two weeks became dominant, being found in 80% of the samples and remaining at this level during all the study periods. The lineage composition of the viral population found in Madrid was more similar to the European population than to the publicly available Spanish data, underlining the role of Madrid as a national and international transport hub. In agreement with this, phylodynamic analysis suggested multiple independent entries before the national lockdown and air transportation restrictions.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on nosocomial Clostridioides difficile infection.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has induced a reinforcement of infection control measures in the hospital setting. Here, we assess the impact of the COVID-19 pandemic on the incidence of nosocomial Clostridioides difficile infection (CDI). METHODS: We retrospectively compared the incidence density (cases per 10,000 patient days) of healthcare-facility-associated (HCFA) CDI in a tertiary-care hospital in Madrid, Spain, during the maximum incidence of COVID-19 (March 11 to May 11, 2020) with the same period of the previous year (control period). We also assessed the aggregate in-hospital antibiotic use (ie, defined daily doses [DDD] per 100 occupied bed days [BD]) and incidence density (ie, movements per 1,000 patient days) of patient mobility during both periods. RESULTS: In total, 2,337 patients with reverse transcription-polymerase chain reaction-confirmed COVID-19 were admitted to the hospital during the COVID-19 period. Also, 12 HCFA CDI cases were reported at this time (incidence density, 2.68 per 10,000 patient days), whereas 34 HCFA CDI cases were identified during the control period (incidence density, 8.54 per 10,000 patient days) (P = .000257). Antibiotic consumption was slightly higher during the COVID-19 period (89.73 DDD per 100 BD) than during the control period (79.16 DDD per 100 BD). The incidence density of patient movements was 587.61 per 1,000 patient days during the control period and was significantly lower during the COVID-19 period (300.86 per 1,000 patient days) (P < .0001). CONCLUSIONS: The observed reduction of ~70% in the incidence density of HCFA CDI in a context of no reduction in antibiotic use supports the importance of reducing nosocomial transmission by healthcare workers and asymptomatic colonized patients, reinforcing cleaning procedures and reducing patient mobility in the epidemiological control of CDI.

False-negative results of initial RT-PCR assays for COVID-19: A systematic review.

BACKGROUND: A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19. METHODS: We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020. RESULTS: We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues. CONCLUSIONS: There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence). SYSTEMATIC REVIEW REGISTRATION: Protocol available on the OSF website: https://tinyurl.com/vvbgqya.