Significant specificity of TruScreen in cervical cytology of ASC and LSIL women with incomplete cervical transformation zone type during COVID-19 post-pandemic in China: a prospective study (preprint)

Objective: To evaluate the efficacy of TruScreen (TS) detecting cervical intraepithelial neoplasia (CIN) in cytology of atypical squamous cells (ASC) and low-grade squamous intraepithelial lesion (LSIL) women during COVID-19 post-pandemic. Design: Prospective, single-center study. Setting: Changsha, China. Population: ASC and LSIL women from December 2020 to May 2021. Methods: Participants underwent TS, colposcopy examination and biopsy in turn. Diagnostic value of TS, high-risk human papillomavirus (hrHPV) and TS combined with hrHPV were compared. Differences of TS regarding cervical transformation zone (TZ) type and menopause, correlations between TS and p16, Ki-67 were assessed. Main outcome measures: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under curve (AUC) for diagnostic value. Spearman coefficient for correlation. Results: A total of 483 patients were enrolled. Specificity of TS detecting CIN1+, CIN2+, CIN3+ were 77.1% (95% CI, 70.4%-82.7%), 66.7% (95% CI, 61.5%-71.5%), 62.7% (95% CI, 57.8%-67.4%) and all were significantly higher than hrHPV test (P<0.001). TS had a high sensitivity (68.0% vs 52.0%, P>0.05) and significantly higher specificity (70.0% vs 48.5%, P<0.05) and NPV (89.6% vs 73.3%, P<0.05) in women with incomplete cervical TZ type (II and III) than TZ type I in detection of CIN2+. Conclusion: TS is an effective triage screening method for cervical cytology of ASC and LSIL women during COVID-19 post-pandemic, especially for incomplete cervical TZ type women. Funding: Supported by National Natural Science Foundation Project of China (81771546) and Hunan Science and Technology Innovation Project (2020SK53404). Keywords: TruScreen; Cervical cancer screening; Cervical transformation zone; CIN; COVID-19.

Development of a prediction model for 30-day COVID-19 hospitalization and death in a national cohort of Veterans Health Administration patients - March 2022 - April 2023. (preprint)

ObjectiveDevelop models to predict 30-day COVID-19 hospitalization and death in the Omicron era for clinical and research applications. Material and MethodsWe used comprehensive electronic health records from a national cohort of patients in the Veterans Health Administration (VHA) who tested positive for SARS-CoV-2 between March 1, 2022, and March 31, 2023. Full models incorporated 84 predictors, including demographics, comorbidities, and receipt of COVID-19 vaccinations and anti-SARS-CoV-2 treatments. Parsimonious models included 19 predictors. We created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. We used the Super Learner ensemble machine learning algorithm to fit prediction models. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), Brier scores, and calibration intercepts and slopes in a 20% holdout dataset. ResultsModels were trained and tested on 198,174 patients, of whom 8% were hospitalized or died within 30 days of testing positive. AUCs for the full models ranged from 0.80 (hospitalization) to 0.91 (death). Brier scores were close to 0, with the lowest error in the mortality model (Brier score: 0.01). All three models were well calibrated with calibration intercepts <0.23 and slopes <1.05. Parsimonious models performed comparably to full models. DiscussionThese models may be used for risk stratification to inform COVID-19 treatment and to identify high-risk patients for inclusion in clinical trials. ConclusionsWe developed prediction models that accurately estimate COVID-19 hospitalization and mortality risk following emergence of the Omicron variant and in the setting of COVID-19 vaccinations and antiviral treatments.

Receipt of anti-SARS-CoV-2 pharmacotherapies among non-hospitalized U.S. Veterans with COVID-19, January 2022 to January 2023 (preprint)

IMPORTANCESeveral pharmacotherapies have been authorized to treat non-hospitalized persons with symptomatic COVID-19. Longitudinal information on their use is needed. OBJECTIVETo analyze trends and factors related to prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA). DESIGN, SETTINGS, AND PARTICIPANTSThis cohort study evaluated non-hospitalized veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023, using VHA and linked Community Care and Medicare databases. EXPOSURESDemographic characteristics, regional and local systems of care including Veterans Integrated Services Networks (VISNs), underlying medical conditions, COVID-19 vaccination. MAIN OUTCOMES AND MEASURESMonthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) was described. Multivariable logistic regression was used to identify factors independently associated with receipt of any versus no COVID-19 pharmacotherapy. RESULTSAmong 285,710 veterans (median [IQR] age, 63.1 [49.9-73.7] years; 247,358 (86.6%) male; 28,444 (10%) Hispanic; 198,863 (72.7%) White; 61,269 (22.4%) Black) who tested positive for SARS-CoV-2 between January 2022 and January 2023, the proportion receiving any pharmacotherapy increased from 3.2% (3,285/102,343) in January 2022 to 23.9% (5,180/21,688) in August 2022, and declined slightly to 20.8% (2,194/10,551) by January 2023. Across VISNs, the range in proportion of test-positive patients who received nirmatrelvir-ritonavir or molnupiravir during January 2023 was 5.9 to 21.4% and 2.1 to 11.1%, respectively. Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR], 1.18, 95% CI 1.14-1.22 for 65 to 74 versus 50 to 64 years; aOR 1.19, 95% CI 1.15-1.23 for 75 versus 50 to 64 years), have a higher Charlson Comorbidity Index (CCI) (aOR 1.52, 95% CI 1.44-1.59 for CCI [≥]6 versus 0), and be vaccinated against COVID-19 (aOR 1.25, 95% CI 1.19-1.30 for primary versus no vaccination; aOR 1.47, 95% CI 1.42-1.53 for booster versus no vaccination). Compared with White veterans, Black veterans (aOR 1.06, 95% CI 1.02 to 1.09) were more likely to receive treatment, and compared with non-Hispanic veterans, Hispanic veterans (aOR 1.06, 95% CI 1.01-1.11) were more likely to receive treatment. CONCLUSIONS AND RELEVANCEAmong veterans who tested positive for SARS-CoV-2 between January 2022 and January 2023, prescription of outpatient COVID-19 pharmacotherapies peaked in August 2022 and declined thereafter. There remain large regional differences in patterns of nirmatrelvir-ritonavir and molnupiravir use.

Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay.

There have been several false-positive results in the antibody detection of COVID-19. This study aimed to analyze the distribution characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin M (IgM) and immunoglobulin G (IgG) in false-positive results using chemiluminescent immunoassay. The characteristics of false-positive results in SARS-CoV-2 IgM and IgG tests were analyzed. The false-positive proportion of single SARS-CoV-2 IgM-positive results was 95.88%, which was higher than those of single SARS-CoV-2 IgG-positive results (71.05%; p < 0.001) and SARS-CoV-2 IgM- and IgG-positive results (39.39%; p < 0.001). The S/CO ratios of SARS-CoV-2 IgM and IgG in false-positive results ranged from 1.0 to 50.0. The false-positive probability of SARS-CoV-2 IgM in the ratios of specimen signals to the cutoff value (S/CO) range (1.0-3.0) was 95.06% (77/81), and the probability of false-positive results of SARS-CoV-2 IgG in the S/CO range (1.0-2.0) was 85.71% (24/28). Dynamic monitoring showed that the S/CO values of IgM in false-positive results decreased or remained unchanged, whereas the S/CO values of IgG in false-positive results decreased. The possibility of false-positive single SARS-CoV-2 IgM-positive and single SARS-CoV-2 IgG-positive results was high. As the value of S/CO ratios decreased, the probability of false-positives consequently increased, especially among the single SARS-CoV-2 IgM-positive results.

Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. Veterans: target trial emulation studies with one-month and six-month outcomes (preprint)

Background: Information about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes during the Omicron surge is limited. We sought to determine the effectiveness of nirmatrelvir-ritonavir and molnupiravir for the outpatient treatment of COVID-19. Methods: We conducted three retrospective target trial emulation studies comparing matched patient cohorts who received nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir in the Veterans Health Administration (VHA). Participants were Veterans in VHA care at risk for severe COVID-19 who tested positive for SARS-CoV-2 in the outpatient setting during January and February 2022. Primary outcomes included all-cause 30-day hospitalization or death and 31-180-day incidence of acute or long-term care admission, death, or post-COVID-19 conditions. For 30-day outcomes, we calculated unadjusted risk rates, risk differences, and risk ratios. For 31-180-day outcomes, we used unadjusted time-to-event analyses. Results: Participants were 90% male with median age 67 years and 26% unvaccinated. Compared to matched untreated controls, nirmatrelvir-ritonavir-treated participants (N=1,587) had a lower 30-day risk of hospitalization (27.10/1000 versus 41.06/1000, risk difference [RD] -13.97, 95% CI -23.85 to -4.09) and death (3.15/1000 versus 14.86/1000, RD -11.71, 95% CI -16.07 to -7.35). Among persons who were alive at day 31, further significant reductions in 31-180-day incidence of hospitalization (sub-hazard ratio 1.07, 95% CI 0.83 to 1.37) or death (hazard ratio 0.61, 95% CI 0.35 to 1.08) were not observed. Molnupiravir-treated participants aged [≥]65 years (n=543) had a lower combined 30-day risk of hospitalization or death (55.25/1000 versus 82.35/1000, RD -27.10, 95% CI -50.63 to -3.58). A statistically significant difference in 30-day or 31-180-day risk of hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants. Incidence of most post-COVID conditions was similar across comparison groups. Conclusions: Nirmatrelvir-ritonavir was highly effective in preventing 30-day hospitalization and death. Short-term benefit from molnupiravir was observed in older groups. Significant reductions in adverse outcomes from 31-180 days were not observed with either antiviral.

Duration of Acute Kidney Injury and In-Hospital Mortality in Elder Patients with Severe COVID-19: A Retrospective Cohort Study.

Background: Patients with severe coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) in the intensive care unit (ICU) have extremely high rates of mortality. This study evaluated the prognostic impact of AKI duration on in-hospital mortality in elder patients. Methods: We performed a retrospective study of 126 patients with confirmed COVID-19 with severe or critical disease who treated in the ICU from February 4, 2020, to April 16, 2020. AKI was defined according to the Kidney Disease Improving Global Outcomes serum creatinine (Scr) criteria. AKI patients were divided into transient AKI and persistent AKI groups based on whether Scr level returned to baseline within 48 h post-AKI. Results: In total, 107 patients were included in the final analysis. The mean age was 70 (64-78) years, and 69 (64.5%) patients were men. AKI occurred in 48 (44.9%) during their ICU stay. Of these, 11 (22.9%) had transient AKI, and 37 (77.9%) had persistent AKI. In-hospital mortality was 18.6% (n = 11) for patients without AKI, 72.7% (n = 8) for patients with transient AKI, and 86.5% (n = 32) for patients with persistent AKI (P < 0.001). Kaplan-Meier curve analysis revealed that patients with both transient AKI and persistent AKI had significantly higher death rates than those without AKI (log-rank P < 0.001). Multivariate Cox regression analysis revealed that transient and persistent AKI were an important risk factor for in-hospital mortality in older patients with severe COVID-19 even after adjustment for variables (hazard ratio [HR] = 2.582; 95% CI: 1.025-6.505; P = 0.044; and HR = 6.974; 95% CI: 3.334-14.588; P < 0.001). Conclusions: AKI duration can be an important predictive parameter in elder patients suffering from COVID-19 and are admitted to ICU. Among these patients, those exhibiting persistent AKI have a lower in-hospital survival rate than those with transient AKI, emphasizing the importance of identifying an appropriate treatment window for early intervention.

Receipt of anti-SARS-CoV-2 pharmacotherapies among U.S. Veterans with mild to moderate COVID-19, January-February 2022 (preprint)

BackgroundOlder adults and persons with medical co-morbidities are at increased risk for severe COVID-19. Several pharmacotherapies demonstrated to reduce the risk of COVID-19-related hospitalization and death have been authorized for use. We describe factors associated with receipt of outpatient COVID-19 pharmacotherapies in the Veterans Health Administration. MethodsWe conducted a retrospective cohort study among Veterans with risk factors for severe COVID-19 who tested positive for SARS-CoV-2 during January and February 2022. We compared receipt of any COVID-19 pharmacotherapy, including sotrovimab, nirmatrelvir plus ritonavir, molnupiravir, or remdesivir versus no antiviral or monoclonal antibody treatment according to demographic characteristics, place of residence, underlying medical conditions, and COVID-19 vaccination using multivariable logistic regression. ResultsDuring January and February 2022, 16,546 courses of sotrovimab, nirmatrelvir, and molnupiravir were allocated across the Veterans Health Administration. Among 111,717 Veterans testing positive for SARS-CoV-2, 4,233 (3.8%) received any COVID-19 pharmacotherapy, including 2,870 of 92,396 (3.1%) in January and 1,363 of 19,321 (7.1%) in February. Among a subset of 56,206 Veterans with documented COVID-19-related symptoms in the 30 days preceding positive SARS-CoV-2 test, 3,079 of 53,206 (5.5%) received any COVID-19 pharmacotherapy. Untreated Veterans had a median age of 60 years (interquartile range [IQR] 46-71 years) and median 3 underlying medical conditions (IQR 2-5). Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR] 1.66, 95% confidence interval [CI] 1.52-1.80, 65-74 versus 50-64 years; aOR 1.67, 95% CI 1.53-1.84 [≥]75 versus 50-64 years) and have a higher number of underlying conditions (aOR 1.63, 95% CI 1.48-1.79, 3-4 versus 1-2 conditions; aOR 2.17, 95% CI 1.98-2.39, [≥]5 versus 1-2 conditions). Persons of Black versus White race (aOR 0.65, 95% CI 0.60-0.72) and well as persons of Hispanic ethnicity (aOR 0.88, 95% CI 0.77-0.99) were less likely to receive treatment. Conclusions and RelevanceAlthough supply of outpatient COVID-19 pharmacotherapies during January and February 2022 was limited, prescription of these pharmacotherapies was underutilized, consistent with early national patterns in dispensing. Racial and ethnic minorities were less likely to receive any pharmacotherapy.

Clinical features of patients with Severe acute respiratory syndrome Coronavirus 2 Delta variant infection and abnormal liver function in Guangdong Province, China. (Theme Issue: New advances in the precise diagnosis and treatment of liver cancer.) [Chinese]

Objective: To investigate the clinical features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection and abnormal liver function in Guangdong Province, China.

Coronavirus disease 2019 (COVID-19) complicated with human immunodeficiency virus (HIV) infection: a case report of nursing experience.

In this paper, we report a case of coronavirus disease 2019 (COVID-19) complicated with human immunodeficiency virus (HIV) infection. The 50-year-old male patient had unexplained "intermittent fever with sore throat" on February 9th, 2020. Chest computed tomography (CT) showed bilateral multiple patchy opacities and ground-glass opacities. A COVID-19 RNA test was positive. After admission, additional laboratory tests revealed the following: white blood cell (WBC) count, 4.7×109/L; neutrophil percentage, 85.1%; lymphocyte percentage, 12.3%; lymphocyte count, 0.59×109/L; hypersensitivity C-reactive protein, 5.52 mg/L; four coagulation factors, +; D-dimer, 1.32 mg/L; and procalcitonin, normal. He was HIV (+). The patient was diagnosed with COVID-19 complicated with HIV infection. The healthcare team administered symptomatic care, including nasal oxygen, oseltamivir, Lianhua Qingwen capsule, moxifloxacin, ribavirin, and thymus faxin, as well as nutritional support, mental care, diet and life management, and close monitoring. Moreover, the team implemented strict disinfection and quarantine and occupational protection. The patient's temperature returned to normal and sore throat significantly improved by day 10, and COVID-19 RNA tests were negative on February 19th, February 21st, and February 22nd. Reexamination by chest CT on February 22nd showed significant absorption of inflammation. After rounds by the chief physician and consultation with specialists, the patient was released from quarantine and discharged on February 23rd per the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 6). Patients with COVID-19 and HIV infection face both physical and mental challenges. More attention should be paid to nursing as we understand more about COVID-19. We hope to share our nursing experience through this case.

Clinical characteristics and risk factors of mortality in elderly patients with novel coronavirus pneumonia

Objective: To explore the clinical characteristics and risk factors of mortality in the elderly patients with novel coronavirus pneumonia(COVID-19).

Pandemic Metric with Confidence (PMC) Model to Predict Trustworthy Probability of Utilized COVID-19 Pandemic Trajectory across the Global (preprint)

Lots of works aim to reveal the driving factors of COVID-19 pandemic trajectory yet ignore the confidence of utilized trajectory data, making consequent results suspicious. Hereby, we proposed a pandemic metric with confidence (PMC) model in the hypothesis of Bernoulli Distribution of nine trajectories reported from 113 countries. Results exhibit the average confidence of trajectories across the global not in excess of 12.1% with the error threshold configuration of 1E-5. In contrast, the 95% high confidence setting also failed to predict the trajectory containing the acceptable error not beyond 1E-3. Thus, a proposed trade-off strategy between two contradictory expections (>50% confidence, <1E-3 error) supports 61% of investigated countries to predict the varying trajectory with confidence beyond 50%. Moreover, PMC model recommend the remanent 39% countries to extend the proportion of populaces in COVID-19 detecting-pool to a suggested-value (>1% of populations), ensuing the average confidence up to 70%.

Respiratory rehabilitation program (draft) of integrated traditional Chinese and western medicine for novel Coronavirus pneumonia (COVID-19)

Since December 2019, a number of cases of pneumonia with unexplained reasons have been reported in Wuhan, Hubei Province, and a large number of cases have been infected. National Health Commission of the People's Republic of China has named it novel coronavirus pneumonia (COVID-19). With the strengthening of prevention and control forces, the number of mild patients in mobile cabin hospital has increased and a large number of patients have been cured and discharged from the hospital. The rehabilitation program of integrated traditional Chinese and Western medicine needs to be formulated and implemented urgently. Therefore, according to treatment protocols issued by National Health Commission of the People's Republic of China and relevant institutes, and widely discussion of relevant experts of pulmonary rehabilitation, TCM and nutrition, Respiratory Rehabilitation Program (Draft) of Integrated Traditional Chinese and Western Medicine for COVID-19 was compiled, in order to play a positive role in the follow-up epidemic prevention and control.

Coronavirus disease 2019 (COVID-19) complicated with acute myocardial infarction: etiology and nursing experience of three case reports.

Coronavirus disease 2019 (COVID-19), an acute infectious disease, which is characterized by influenza, fever, cough and dyspnea. Up to now, the pathogenic mechanism and radical cure treatment for COVID-19 are still unknown. However, COVID-19 could lead to pneumonia, multiple organ failure and even death with disease development. During the period of February 10 and March 26, 2020, we admitted and treated three COVID-19 patients complicated with acute myocardial infarction. As we all know, acute myocardial infarction is a kind of disease that induces myocardial ischemia necrosis and leads to high mortality. Through the three COVID-19 patients complicated with acute myocardial infarction, we have strengthened our nursing experience. Thus, we wish to share our nursing experience with these cases by analyzing the etiology of three patients with coronavirus disease 2019 (COVID-19) complicated with acute myocardial infarction in this paper. First, we retrospectively analyzed the clinical data, including patient complaints, diagnosis, treatment, and prognosis, of three patients with COVID-19 complicated with acute myocardial infarction admitted to Ward II, Department of Infectious Diseases III, Huoshenshan Hospital, Wuhan, Hubei Province, China, between February 10 and March 26, 2020. Then, we searched for relevant literature, analyzed etiology, and summarized the nursing measures taken. For COVID-19 patients with a high risk of acute myocardial infarction, nurses should stay vigilant, closely monitor any change in condition, and implement early measures to maintain vital signs and enable timely visits with specialists. Finally, we importantly found that these nursing measures are keys to managing the patient's condition, improving patient outcomes, and increasing the chance of treatment success.

Neutralizing antibodies targeting SARS-CoV-2 spike protein.

SARS-CoV-2 causing the worldwide pandemic has changed people's life in multiple aspects dramatically since it's first identified in Wuhan, China at the end of 2019. While the numbers of infected patients and death toll keep vigorous increasing, curbing the progression of the pandemic is an urgent goal. Efforts have been made to search for prophylactic and therapeutic approaches including neutralizing antibodies development. By reviewing dozens of studies on anti-spike antibodies identification, we concluded that (1) promising therapeutic antibodies are being fished out by various approaches, such as screening of single B cells of convalescent patients, recombinant antibody library and B cells of immunized animals; (2) the epitopes are mainly RBD, but also some non-RBD domains, without the requisite of overlapping with ACE2 binding sites; (3) Neutralizing antibodies are convergent to a few germline genes, including IGHV3-30, IGHV3-53, IGHV3-66, with varying levels of somatic mutations. This review summarizes the progress in neutralizing antibodies development and the germline enrichment of effective antibodies, which will shed light on COVID-19 treatment and vaccine design.

COVID-19: Comparison between 8-days and extended 4-weeks outbreak periods through socioeconomic and natural factors (preprint)

Since mid-March 2020, global COVID-19 pandemic has experienced an exponential growth in process from sporadic to sudden outbreaks. This paper selects the 8-day surge data of daily cases, death and recovery rates (March 19-26, 2020) from 18 countries with severe pandemic situation to discuss the impact of 9 factors of both socioeconomic and natural on the pathogen outbreak. Moreover, the paper also elaborates analysis and comparison of relatively slow 4-week (February 1-29, 2020) data of China's surge cases to determine the relationship between social and natural factors and on the spread of pandemic, which provides an effective reference for delaying and controlling the pandemic development.