Virus Clearance Time Research Articles

Comparable Efficacy of Lopinavir/Ritonavir and Remdesivir in Reducing Viral Load and Shedding Duration in Patients with COVID-19.

The spread of COVID-19 has significantly increased research on antiviral drugs and measures such as case isolation and contact tracing. This study compared the effects of lopinavir/ritonavir and remdesivir on COVID-19 patients with a control group receiving no antiviral drugs. Patients confirmed to have a SARS-CoV-2 infection via real-time RT-PCR were divided into three groups: lopinavir/ritonavir, remdesivir, and control. We assessed the efficacy of these drugs in reducing viral load and viral shedding duration using real-time RT-PCR and Vero E6 cell cultures. Lopinavir/ritonavir led to no detectable infectious SARS-CoV-2, with a median viral clearance time of one day, whereas one remdesivir-treated case remained culture-positive until day 12. Lopinavir/ritonavir significantly reduced viral load compared to remdesivir and control groups (p = 0.0117 and p = 0.0478). No infectious virus was detected in the lopinavir/ritonavir group, and the non-infectious SARS-CoV-2 proportion remained constant at 90%, higher than in the remdesivir and control groups (p = 0.0097). There was a significant difference in culture positivity among the groups (p = 0.0234), particularly between the lopinavir/ritonavir and remdesivir groups (p = 0.0267). These findings suggest that lopinavir/ritonavir reduces viral load and shortens the viral shedding duration compared to remdesivir, despite not being an effective treatment option.

Favipiravir does not improve viral clearance in mild to moderate COVID-19 – A systematic review and meta-analysis of randomized controlled trials

PurposeFavipiravir has been used in the therapy of COVID-19, including patients with mild to moderate symptoms in certain countries. The aim of our systematic review and meta-analysis was to investigate its efficacy and safety in mild-to-moderate COVID-19 infections. MethodsThe PubMed, Embase, Web of Science, and Cochrane databases were systematically reviewed for articles reporting the results of randomized controlled trials published until January 6, 2023, resulting in the identification of 20 eligible studies. ResultsThere were no significant differences in viral clearance time (HR = 1.20, p = 0.09) compared to those without favipiravir therapy. However, in the subgroup analyses, favipiravir treatment significantly increased viral clearance by 59 % (HR = 1.59, p < 0.01) and 42 % (HR = 1.42, p < 0.01], I2 = 20 %) compared to the comparator group in patients with moderate severity of COVID-19 and in the inpatient care setting, respectively. Favipiravir had no beneficial effects in the case of patients with mild symptoms and treated in ambulatory care. ConclusionsThe use of favipiravir is questionable in the treatment of outpatients with COVID-19 with mild symptoms. Moderate beneficial effects in the case of patients with moderate symptoms and inpatients should be treated with care due to the limitations of the analysed trials.

Risk factors for progression to severe infection and prolonged viral clearance time in hospitalized elderly patients infected with the Omicron variant of SARS-CoV-2: a retrospective study at Shanghai Fourth People's Hospital, School of Medicine, Tongji University.

In elderly patients infected with the Omicron variant, disease progression to severe infection can result in poor outcomes. This study aimed to identify risk and protective factors associated with disease progression to severe infection and viral clearance time in elderly Omicron-infected patients. Shanghai Fourth People's Hospital, School of Medicine, Tongji University, was officially designated to provide treatment to patients with COVID-19. This study was conducted on confirmed Omicron cases admitted to the hospital between 10 April 2022 and 21 June 2022. In total, 1,568 patients aged 65 years or older were included. We conducted a retrospective, observational study using logistic regression to analyze risk and protective factors for the development of severe disease and Cox proportional hazards regression models to analyze factors influencing viral clearance time. Aged over 80 years, having 2 or more comorbidities, combined cerebrovascular disease, chronic neurological disease, and mental disorders were associated with the development of severe disease, and full vaccination was a protective factor. Furthermore, aged over 80 years, combined chronic respiratory disease, chronic renal disease, cerebrovascular disease, mental disorders, and high viral load were associated with prolonged viral clearance time, and full vaccination was a protective factor. This study analyzed risk factors for progression to severe infection and prolonged viral clearance time in hospitalized elderly Omicron-infected patients. Aged patients with comorbidities had a higher risk of developing severe infection and had longer viral clearance, while vaccination protected them against the Omicron infection.

Dynamics of viral DNA shedding and culture viral DNA positivity in different clinical samples collected during the 2022 mpox outbreak in Lombardy, Italy

BackgroundMpox virus (MPXV) has recently spread outside of sub-Saharan Africa. This large multicentre study was conducted in Lombardy, the most densely populated Italian region accounting for more than 40% of Italian cases. The present study aims to: i) evaluate the presence and the shedding duration of MPXV DNA in different body compartments correlating the MPXV viability with the time to onset of symptoms; ii) provide evidence of MPXV persistence in different body compartment as a source of infection and iii) characterize the MPXV evolution by whole genome sequencing (WGS) during the outbreak occurred in Italy. Material and methodsThe study included 353 patients with a laboratory-confirmed diagnosis of MPXV infection screened in several clinical specimens in the period May 24th - September 1st, 2022. Viral isolation was attempted from different biological matrices and complete genome sequencing was performed for 61 MPXV strains. ResultsMPXV DNA detection was more frequent in the skin (94.4%) with the longest median time of viral clearance (16 days). The actively-replicating virus in cell culture was obtained for 123/377 (32.6%) samples with a significant higher viral quantity on isolation positive samples (20 vs 31, p < 0.001). The phylogenetic analysis highlighted the high genetic identity of the MPXV strains collected, both globally and within the Lombardy region. ConclusionSkin lesion is gold standard material and the high viral load and the actively-replicating virus observed in genital sites confirms that sexual contact plays a key role in the viral transmission.

Significance of saline nasalirrigation for COVID-19 infection: observations and reflections from nursing care of nasopharyngeal carcinoma.

Coronavirus disease 2019 (COVID-19) has placed a tremendous burden on the world's healthcare systems, prompting medical professionals worldwide to diligently research and experiment with treatment methods to prevent infection and alleviate symptoms. Previous studies have shown the potential of nasal irrigation in reducing viral clearance time and alleviating local symptoms of COVID-19. However, views differ regarding its efficacy in improving systemic symptoms. Thus, we sought to examine whether saline nasal irrigation might play a role in treatment and self-care after COVID-19 infection, but further validation is still necessary. We conducted a retrospective analysis of 468 patients and 51 healthcare personnel concurrently. The participants were grouped based on whether they received saline nasal irrigation. We used χ2 tests and Fisher's exact tests to assess the differences in the rates of COVID-19 infection and the rates of developing a fever after COVID-19 infection among different groups. Additionally, we used independent samples t-tests and Mann-Whitney U tests to evaluate differences in the maximum fever temperature and fever duration among participants with fever in different groups. The rate of developing a fever after COVID-19 infection was lower (37.7%) in the patients who underwent saline nasal irrigation. Among all febrile patients, there was no difference in the highest fever temperature, but patients who underwent saline nasal irrigation had a shorter fever duration (1.72±1.05 days). Additionally, the rate of COVID-19 infection and the rate of developing a fever were higher, and fever symptoms were more severe in the healthcare worker group than in the patient group. Saline nasal irrigation can alleviate symptoms caused by COVID-19 infection.

Clinical and prognostic implications of hyaluronic acid in patients with COVID-19 reinfection and first infection.

Previous research has shown that human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promote coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA). However, the association of HA with mortality and long COVID in SARS-CoV-2 reinfection and first infection is unclear. Patients with COVID-19 at Beijing Ditan Hospital from September 2023 to November 2023 were consecutively enrolled. SARS-CoV-2 reinfections were matched 1:2 with first infections using a nearest neighbor propensity score matching algorithm. We compared the hospital outcomes between patients with COVID-19 reinfection and first infection. The association between HA levels and mortality and long COVID in the matched cohort was analyzed. The reinfection rate among COVID-19 hospitalized patients was 25.4% (62 cases). After propensity score matching, we found that reinfection was associated with a better clinical course and prognosis, including lower levels of C-reactive protein and erythrocyte sedimentation rate, fewer cases of bilateral lung infiltration and respiratory failure, and shorter viral clearance time and duration of symptoms (p < 0.05). HA levels were significantly higher in patients with primary infection [128.0 (90.5, 185.0) vs. 94.5 (62.0, 167.3), p = 0.008], those with prolonged viral clearance time [90.5 (61.5, 130.8) vs. 130.0 (95.0, 188.0), p < 0.001], and deceased patients [105.5 (76.8, 164.5) vs. 188.0 (118.0, 208.0), p = 0.002]. Further analysis showed that HA was an independent predictor of death (AUC: 0.789), and the risk of death increased by 4.435 times (OR = 5.435, 95% CI = 1.205-24.510, p = 0.028) in patients with high HA levels. We found that patients with HA levels above 116 ng/mL had an increased risk of death. However, the incidence of long COVID was similar in the different HA level groups (p > 0.05). Serum HA may serve as a novel biomarker for predicting COVID-19 mortality in patients with SARS-CoV-2 reinfection and first infection. However, HA levels may not be associated with long COVID.

A Retrospective Study on COVID-19 Infections Caused by Omicron Variant with Clinical, Epidemiological, and Viral Load Evaluations in Breakthrough Infections.

Purpose: To explore the clinical, epidemiological, and viral load characteristics of COVID-19 caused by the omicron variant. Methods: Based on the COVID-19 epidemic caused by SARS-CoV-2 Omicron BA.2 broke out in Shanghai, China. To analyze whether there is any association between clinical symptoms and viral load of COVID-19 with age, sex, and combined disease and whether the clinical symptoms and viral load are associated with vaccine-breakthrough infections. Results: The most common symptoms were cough, expectoration, and fatigue, which were more common in women than males (p < 0.001). The average viral clearance time in the > 75 years group was the longest (6.64 days). The viral load in the 60-75 years group was significantly higher than that in the other groups (p < 0.001). The 18-45 years old group had the most clinical symptoms at admission (45.39%). The days of nucleic acid-negative conversion, average viral load, highest viral load, and clinical symptoms in comorbid chronic disease patients are longer (p < 0.001). The average and highest viral loads in the unvaccinated group were longer than those in the vaccine breakthrough infection groups (p < 0.001). However, the clinical symptoms in the vaccine breakthrough infection group were significantly more severe than those in the unvaccinated group (p < 0.001). Conclusions: We found that female patients, the elderly, and those with underlying comorbidities had longer clinical positive symptoms and viral loads. Although vaccination may not reduce clinical symptoms, it can shorten the viral load and the time required for virus clearance.

Adhatoda vasica and Tinospora cordifolia extracts ameliorate clinical and molecular markers in mild COVID-19 patients: a randomized open-label three-armed study

BackgroundSARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19.MethodsA total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19–65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A (Adhatoda vasica; AV; 500 mg; n = 50); Group B (Tinospora cordifolia; TC; 500 mg; n = 43), and Group C (AV + TC; 250 mg each; n = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes.ResultsWe found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85–14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14–14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62–13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced.ConclusionsAll the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects.Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27Graphical

Efficacy and safety of molnupiravir in patients with Omicron variant vaccine breakthrough COVID-19 infection: a randomized, controlled trial.

Introduction: Randomized, controlled trials of molnupiravir in real-world use during the Omicron wave are scarce. The frequency of hospitalization and death is low, so further research is needed to confirm the virological efficacy of molnupiravir. Methods: A single-center, randomized, controlled clinical trial was conducted, and 111 hospitalized coronavirus disease 2019 (COVID-19) patients were randomly assigned at a ratio of 1:1. Fifty-three patients in the molnupiravir group were administered 800mg of molnupiravir twice daily for 5 days in addition to the standard therapy, and 58 patients in the control group only received the standard therapy in accordance with local guidelines. The antiviral effect and adverse events were evaluated during the follow-up. Results: The median viral clearance time in the molnupiravir group was significantly shorter than that in the control group (p = 0.003). Furthermore, patients who started molnupiravir therapy within 3 days had significantly shorter viral clearance time than the controls (p = 0.003). In the vaccinated subgroup, molnupiravir therapy was also associated with a shorter viral clearance time (p = 0.003). A total of three adverse events, which were minor, were reported in the molnupiravir group. One of the patients had mild liver function abnormalities, and all of them were resolved without intervention. However, the remission time was similar between the two tested groups. Conclusion: Molnupiravir exhibited good viral replication inhibitor efficacy in patients with Omicron variant vaccine breakthrough COVID-19 infection. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR2200059796].

Viral kinetics of sequential SARS-CoV-2 infections

The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we identified 71 individuals with two well-sampled SARS-CoV-2 infections between March 11th, 2020, and July 28th, 2022. We compared the SARS-CoV-2 viral kinetics of first vs. second infections in this group, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a faster clearance time. Furthermore, a person’s relative (rank-order) viral clearance time, compared to others infected with the same variant, was roughly conserved across first and second infections, so that individuals who had a relatively fast clearance time in their first infection also tended to have a relatively fast clearance time in their second infection (Spearman correlation coefficient: 0.30, 95% credible interval (0.12, 0.46)). These findings provide evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person’s relative ability to clear SARS-CoV-2 infection that persists across sequential infections.

Clinical analysis of prolonged viral clearance time in patients with lymphoma combined with novel coronavirus infection.

Objective: To compare the period of viral clearance and its influencing factors after severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection between patients with lymphoma and lung cancer. Methods: We retrospectively collected the clinical data of patients with lymphoma and lung cancer (118 cases) diagnosed with SARS-CoV-2 infection and hospitalized in the First Affiliated Hospital of Anhui Medical University between 1 December 2022, and 15 March 2023. Finally, 87 patients with prolonged virus clearance times were included and divided into lymphoma (40 cases) and lung cancer (47 cases) groups. We used the Kaplan-Meier method to draw a negative turn curve. We performed a univariate analysis of the prolongation of virus clearance time and a Cox regression model for multivariate analysis. Results: The median times for viral clearance in the lung cancer and lymphoma groups were 18 (95% confidence interval [CI] 15.112-20.888) and 32 (95%CI 27.429-36.571) days, respectively. Log-rank analysis showed a statistically significant difference (p = 0.048), and the lymphocyte count in the lymphoma group was lower than that in the lung cancer group (p = 0.044). We used the Cox regression model to conduct a multivariate analysis, which revealed that in lymphoma patients, the interval between the time of diagnosis and the time of SARS-CoV-2 infection <24months (hazard ratio [HR]: 0.182, 95%CI: 0.062-0.535, p = 0.02), an interval between the last anti-CD20 monoclonal antibody treatment and the time of SARS-CoV-2 infection of <2months (HR: 0.101, 95%CI: 0.029-0.358, p < 0.001), and a decrease in peripheral blood lymphocyte levels (HR: 0.380, 95%CI: 0.179-0.808, p = 0.012) were independent risk factors for prolonged viral clearance time. Conclusion: Patients with lymphoma combined with SARS-CoV-2 infection had a longer virus clearance time than did patients with lung cancer. Moreover, the lymphocyte count in the lymphoma group was lower than that in the lung cancer group; therefore, the immune status of patients with lymphoma is lower than that of patients with lung cancer. An interval between lymphoma diagnosis and SARS-CoV-2 infection of <2years, anti-CD20 monoclonal antibody treatment within the past 2months, and a decrease in lymphocyte levels in the peripheral blood prolonged the virus clearance time in the patients in this study.

Antiviral efficacy of RAY1216 monotherapy and combination therapy with ritonavir in patients with COVID-19: a phase 2, single centre, randomised, double-blind, placebo-controlled trial

This study aimed to evaluate the efficacy and safety of RAY1216, a novel inhibitor of 3-chymotrypsin-like cysteine protease (3CLpro), in adults with coronavirus disease 2019 (COVID-19). This phase 2, single centre, randomised, double-blind, placebo-controlled trial included hospitalised patients between August 14, 2022, and September 26, 2022, in Sanya Central Hospital (The Third People's Hospital of Hainan Province) in China with no severe symptoms if they had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for not more than 120h (5 days) and a real-time quantitative polymerase chain reaction (qPCR) cycle threshold (Ct) value of ≤30 for both the open reading frames 1ab (ORF1ab) and nucleocapsid (N) genes within 72h before randomisation. Half of the participants (n=30) were randomly assigned (2:1) to receive either RAY1216 or a matched placebo three times a day (TID) for 5 days (15 doses in total), while the other half received RAY1216 plus ritonavir (RAY1216 plus RTV) or a matched placebo every 12h for 5 days (10 doses in total). The primary endpoint was the time of viral clearance. Secondary outcomes included the changes of the SARS-CoV-2 RNA viral load, the positivity rate of the nucleic acid test, and the recovery time of clinical symptoms. A safety evaluation was performed to record and analyse all adverse events that occurred during and after drug administration as well as any cases in which dosing was halted because of these events. Clinicaltrials.gov identifier: ChiCTR2200062889. The viral shedding times in the RAY1216 and RAY1216 plus RTV groups were 166h (95% confidence interval (CI): 140-252) and 155h (95%CI: 131-203), respectively, which were 100h (4.2 days) and 112h (4.6 days) shorter than that of the placebo group, respectively (RAY1216 group vs. Placebo p=0.0060, RAY1216 plus RTV group vs. Placebo p=0.0001). At 24h, 72h, and 120h after administration, the viral RNA loads in the RAY1216 and RAY1216 plus RTV groups were significantly less than those of the placebo groups. At 280h (11.5 days) after administration, the nucleic acid test results in the RAY1216 and RAY1216 plus RTV groups were both negative. The common adverse events related to the investigational drugs were mild and self-limiting laboratory examination abnormalities. Our findings suggest that RAY1216 monotherapy and RAY1216 plus ritonavir both demonstrated significant antiviral activity and reduced the duration of COVID-19 while maintaining a satisfactory safety profile. Considering the limited clinical application of RTV, it is recommended to use RAY1216 alone to further verify its efficacy and safety. This study was sponsored by the Key Research and Development Program of China (2022YFC0868700).

Struggling with COVID-19 in Adult Inborn Errors of Immunity Patients: A Case Series of Combination Therapy and Multiple Lines of Therapy for Selected Patients.

The SARS-CoV-2 infection is now a part of the everyday lives of immunocompromised patients, but the choice of treatment and the time of viral clearance can often be complex, exposing patients to possible complications. The role of the available antiviral and monoclonal therapies is a matter of debate, as are their effectiveness and potential related adverse effects. To date, in the literature, the amount of data on the use of combination therapies and on the multiple lines of anti-SARS-CoV-2 therapy available to the general population and especially to inborn error of immunity (IEI) patients is small. Here, we report a case series of five adult IEI patients managed as inpatients at three Italian IEI referral centers (Rome, Treviso, and Cagliari) treated with combination therapy or multiple therapeutic lines for SARS-CoV-2 infection, such as monoclonal antibodies (mAbs), antivirals, convalescent plasma (CP), mAbs plus antiviral, and CP combined with antiviral. This study may support the use of combination therapy against SARS-CoV-2 in complicated IEI patients with predominant antibody deficiency and impaired vaccine response.

Predictive value of immunoglobulin G, activated partial thromboplastin time, platelet, and indirect bilirubin for delayed viral clearance in patients infected with the Omicron variant.

Omicron is the recently emerged highly transmissible severe acute respiratory syndrome coronavirus 2 variant that has caused a dramatic increase in coronavirus disease-2019 infection cases worldwide. This study was to investigate the association between demographic and laboratory findings, and the duration of Omicron viral clearance. Approximately 278 Omicron cases at the Ruijin Hospital Luwan Branch, Shanghai Jiaotong University School of Medicine were retrospectively analyzed between August 11 and August 31, 2022. Demographic and laboratory data were also collected. The association between demographics, laboratory findings, and duration of Omicron viral clearance was analyzed using Pearson correlation analysis and univariate and multivariate logistic regression. Univariate logistic regression analyses showed that a prolonged viral clearance time was significantly associated with older age and lower immunoglobulin (Ig) G and platelet (PLT) levels. Using multinomial logistic regression analyses, direct bilirubin, IgG, activated partial thromboplastin time (APTT), and PLT were independent factors for longer viral shedding duration. The model combining direct bilirubin, IgG, APTT, and PLT identifies patients infected with Omicron whose viral clearance time was ≥7 days with 62.7% sensitivity and 83.4% specificity. These findings suggest that direct bilirubin, IgG, PLT, and APTT are significant risk factors for a longer viral shedding duration in patients infected with Omicron. Measuring levels of direct bilirubin, IgG, PLT, and APTT is advantageous to identify patients infected with Omicron with longer viral shedding duration.

Nasal spray of an IgM-like ACE2 fusion protein HH-120 accelerates SARS-CoV-2 clearance: A single-center propensity score-matched cohort study.

HH-120, a recently developed IgM-like ACE2 fusion protein with broad-spectrum neutralizing activity against all ACE2-utilizing coronaviruses, has been developed as a nasal spray for use as an early treatment agent to reduce disease progression and airborne transmission. The objective of this study was to evaluate the safety and efficacy of the HH-120 nasal spray in SARS-CoV-2-infected subjects. Eligible symptomatic or asymptomatic SARS-CoV-2-infected participants were enrolled in a single-arm trial to receive the HH-120 nasal spray for no longer than 6 days or until viral clearance at a single hospital between August 3 and October 7, 2022. An external control was built from real-world data of SARS-CoV-2-infected subjects contemporaneously hospitalized in the same hospital using a propensity score matching (PSM) method. After PSM, 65 participants in the HH-120 group and 103 subjects with comparable baseline characteristics in the external control group were identified. The viral clearance time was significantly shorter in participants receiving the HH-120 nasal spray than that in subjects of the control group (median 8 days vs. 10 days, p < 0.001); the difference was more prominent in those subgroup subjects with higher baseline viral load (median 7.5 days vs. 10.5 days, p < 0.001). The incidence of treatment-emergent adverse eventsand treatment-related adverse eventsof HH-120 group were 35.1% (27/77) and 3.9% (3/77), respectively. All the adverse events observed were mild, being of CTCAE grade 1 or 2, and transient. The HH-120 nasal spray showed a favorable safety profile and promising antiviral efficacy in SARS-CoV-2-infected subjects. The results from this study warrant further assessment of the efficacy and safety of the HH-120 nasal spray in large-scale randomized controlled clinical trials.

Clinical efficacy analysis of paxlovid in children with hematological diseases infected with the omicron SARS-CoV-2 new variant.

To summarize the clinical characteristics of children with hematological malignancies co-infected with novel coronavirus and explore the safety and effectiveness of Paxlovid treatment. From December 10, 2022, to January 20, 2023, the clinical data of children with hematological diseases diagnosed with novel coronavirus infection in the outpatient and emergency department of the Seventh Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. According to whether to give paxlovid or not, it is divided into group A (paxlovid group) and group B (non-paxlovid group). The length of fever was 1-6 days in group A and 0-3 days in group B. The viral clearance time was shorter in group A than in group B. The inflammatory indexes CRP and PCT were significantly higher in group A than in group B (P < 0.05). Twenty patients were followed up for 1 month after leaving the hospital, and there were 5 cases of reappearance of fever, 1 case of increased sleep, 1 case of physical fatigue and 1 case of loss of appetite within 2 weeks. Paxlovid has no apparent adverse reactions in children 12 years old and younger with underlying hematological diseases infected with the new coronavirus. Focusing on the interaction between paxlovid and other drugs is necessary during the treatment.

Severe COVID-19: Drugs and Clinical Trials.

By January of 2023, the COVID-19 pandemic had led to a reported total of 6,700,883 deaths and 662,631,114 cases worldwide. To date, there have been no effective therapies or standardized treatment schemes for this disease; therefore, the search for effective prophylactic and therapeutic strategies is a primary goal that must be addressed. This review aims to provide an analysis of the most efficient and promising therapies and drugs for the prevention and treatment of severe COVID-19, comparing their degree of success, scope, and limitations, with the aim of providing support to health professionals in choosing the best pharmacological approach. An investigation of the most promising and effective treatments against COVID-19 that are currently available was carried out by employing search terms including "Convalescent plasma therapy in COVID-19" or "Viral polymerase inhibitors" and "COVID-19" in the Clinicaltrials.gov and PubMed databases. From the current perspective and with the information available from the various clinical trials assessing the efficacy of different therapeutic options, we conclude that it is necessary to standardize certain variables-such as the viral clearance time, biomarkers associated with severity, hospital stay, requirement of invasive mechanical ventilation, and mortality rate-in order to facilitate verification of the efficacy of such treatments and to better assess the repeatability of the most effective and promising results.

The effect of nirmatrelvir-ritonavir on viral clearance and length of hospital stay in patients infected with SARS-CoV-2 omicron variants.

The pandemic of coronavirus disease 2019 (COVID-19) has caused heavy burdens on national healthcare systems. Nirmatrelvir-ritonavir (Paxlovid) may be one of the most promising therapeutic drugs, with reports of up to 89% reduction rates in hospitalization risk and death among patients with mild-to-moderate COVID-19 who are at risk of developing severe disease. However, limited studies have investigated the effects of this class of drugs on viral clearance and length of hospital stay. In this study, we retrospectively analyzed the characteristics of patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and investigated the effects of oral nirmatrelvir-ritonavir on viral clearance and length of hospital stay in mild-to-moderate COVID-19 patients at high risk for progression to severe disease. The median SARS-CoV-2 negative conversion time was 16 (13-20) versus 13 (10-16)days (control group versus nirmatrelvir-ritonavir group, p< 0.001), the median length of hospital stay was 13 (10-16) versus 12 (13-14) days (control group versus nirmatrelvir-ritonavir group, p = 0.01), and the SARS-CoV-2 negative conversion time and length of hospital stay were significantly shorter in the nirmatrelvir-ritonavir group than in the control group. When controlling for hypertension, chronic kidney disease, severity status of COVID-19, use of antibiotic agent, and COVID-19 vaccine received, multiple stepwise linear regression analysis showed that nirmatrelvir-ritonavir treatment was negatively associated with the SARS-CoV-2 negative conversion time and length of hospital stay. Nirmatrelvir-ritonavir reduces the viral clearance time and length of hospital stay in hospitalized patients with COVID-19. Nirmatrelvir-ritonavir might be a promising drug to reduce the virus load and the heavy burden of healthcare systems.

Nirmatrelvir-ritonavir therapy and COVID-19 vaccination improve clinical outcomes of SARS-CoV-2 Omicron variant infection.

To evaluate the effect of Nirmatrelvir-ritonavir therapy and coronavirus disease 2019(COVID-19) vaccination on clinical outcomes of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Omicron infection, we retrospectively analyzed the clinical data of 762 adult patients with confirmed Omicron BA2.2 variant infection, of them 488 patients received standard therapy and 274 patients received Nirmatrelvir-ritonavir therapy. Subjects were matched by propensity score matching using R language, the baseline factors were balanced by the nearest-neighbor matching method and were compared, together with the factors including progression to severe/critical disease, viral clearance time, length of hospital stay, and virological rebound of SARS-CoV-2 infection. Nirmatrelvir-ritonavir therapy significantly accelerated viral clearance at Days 14 and 28 during hospitalization, but it had no impact on disease progression, length of hospital stay, or infection rebound. In contrast, COVID-19 vaccination before admission was positively correlated with the viral clearance rate and negatively correlated with disease progression in a dose-dependent way. COVID-19 vaccination reduced the probability of infection rebound. Other factors such as the number of comorbidities, pneumonia on-admission, and high D2 levels were positively correlated with disease progression. Our study strongly recommended booster COVID-19 vaccination for the elderly population, particularly patients with comorbidities to prevent critical disease.

The value of age IgG and IL6 in estimating time of viral clearance in asymptomatic or mild patients with COVID-19.

The aim of this study was to investigate the relationship between Age, immunoglobin G (IgG), immunoglobin M (IgM), procalcitonin (PCT), and interleukin-6 (IL6), and the time to clear viral nucleic acids in asymptomatic and mild coronavirus disease 2019 (COVID-19) patients, as well as evaluated the predictive value of these biochemical indicators. We performed a retrospective analysis on 1,570 individuals who were admitted to Tianjin First Central Hospital and diagnosed with asymptomatic or mild cases. Laboratory data were collected, including age, gender, levels of IgG, IgM, PCT and IL6, as well as results of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleic acid test. These data were statistically analyzed using SPSS software, version 24.0. The results indicated that among mild patients, Age, IgG, and the time to clear viral nucleic acids were higher than asymptomatic patients (p < 0.05). And the time to clear viral nucleic acids was significantly correlated with Age, IgG, IgM, PCT, and IL6 (p < 0.05), IgG (r = -0.445, p < 0.001) showed moderate correlations. Using logistic regression analysis, we identified older age, high IL6 levels, and low IgG levels were risk factors for nucleic acid clearance exceeding 14 days (p < 0.05). When combining these three indicators to predict the probability of nucleic acid clearance exceeding 14 days in the 1,570 patients, the AUROC was found to be 0.727. Age, IgG, and IL6 could potentially serve as useful predictors for nucleic acid clearance exceeding 14 days in asymptomatic and mild COVID-19 patients.