Clinical effectiveness of nirmatrelvir plus ritonavir on the short- and long-term outcome in high-risk children with COVID-19.

This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.

Association between vitamin D deficiency and post-acute outcomes of SARS-CoV-2 infection.

OBJECTIVES: This study aimed to investigate the association between vitamin D deficiency (VDD) and post-acute outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: This retrospective study used the TriNetX research network to identify COVID-19 patients between January 1 and November 30, 2022. Patients were matched using propensity score matching (PSM) and divided into VDD (< 20 ng/mL) and control (≥ 20 ng/mL) groups. The primary outcome was a composite of post-COVID-19 condition (identified by ICD-10 code), all-cause emergency department (ED) visits, hospitalization, and death during the follow-up period (90-180 days) after the diagnosis of COVID-19. RESULTS: From an initial recruitment of 42,674 non-hospitalized patients with COVID-19 and known 25(OH)D status, a VDD group of 8300 was identified and propensity matched with 8300 controls. During the follow-up period, the VDD group had a higher risk of the primary outcome than did the control group [hazard ratio (HR) = 1.122; 95% confidence interval (CI) = 1.041-1.210]. The VDD group also had a higher risk of all-cause ED visits (HR = 1.114; 95% CI = 1.012-1.226), all-cause hospitalization (HR = 1.230; 95% CI = 1.105-1.369), and all-cause death (HR = 1.748; 95% CI = 1.047-2.290) but not post-COVID-19 condition (HR = 0.980; 95% CI = 0.630-1.523), individually. CONCLUSION: Among the COVID-19 patients, VDD might be associated with a higher risk of all-cause ED visits, hospitalization, and death during the post-acute phase.

Comparison of post-acute sequelae following hospitalization for COVID-19 and influenza.

BACKGROUND: Few studies have directly compared the risk and magnitude of post-acute sequelae following COVID-19 and influenza, and most of these studies were conducted before emergence of the Omicron. This study investigated the prevalence of post-COVID conditions and the long-term risk of emergency department (ED) visits, hospitalizations, and deaths in patients with COVID-19 and compared their risk with that of patients with influenza. METHODS: A retrospective study based on the TriNetX databases, a global health research network. We identified patients with COVID-19 and influenza who required hospitalization between January 1, 2022, and January 1, 2023. We compared the risk of developing any post-COVID conditions between the two groups and also analyzed each post-COVID-19 condition and all-cause ED visits, hospitalizations, and deaths in both populations during the follow-up 90-180 days. RESULTS: Before matching, 7,187 patients with COVID-19 were older (63.9 ± 16.7 vs. 55.4 ± 21.2) and were predominantly male (54.0% vs. 45.4%), and overweight/obese (16.1% vs. 11.2%) than 11,266 individuals with influenza. After propensity score matching, 6,614 patients were identified in each group, resulting in well-balanced baseline characteristics. During follow-up, the COVID-19 group had a higher incidence of any post-COVID-19 condition when compared with the influenza group (17.9% vs. 13.0%), with a hazard ratio (HR) of 1.398 (95% CI, 1.251-1.562). Compared to the influenza group, the COVID-19 group had a significantly higher incidence of abnormal breathing (HR, 1.506; 95% CI, 1.246-1.822), abdominal symptoms (HR, 1.313; HR, 1.034-1.664), fatigue (HR, 1.486; 95% CI, 1.158-1.907), and cognitive symptoms (HR, 1.815; 95% CI, 1.235-2.668). Moreover, the COVID-19 group had a significantly higher risk of the composite outcomes during all-cause ED visits, hospitalizations, and deaths when compared with the influenza group (27.5% vs. 21.7; HR, 1.303; 95% CI, 1.194-1.422). CONCLUSIONS: This study indicates that hospitalized COVID-19 patients are at a higher risk of long-term complications when compared with influenza survivors.

Post-COVID-19 condition risk in patients with intellectual and developmental disabilities: a retrospective cohort study involving 36,308 patients.

BACKGROUND: To date, no studies have investigated the prevalence of post-COVID-19 conditions in patients with Intellectual and Developmental Disabilities (IDD). Addressing this research gap is crucial, as understanding post-COVID-19 conditions in IDD patients can improve care planning, and it is essential not to overlook this vulnerable population in COVID-19 studies. This study was aimed at investigating the prevalence of post-COVID-19 conditions in patients with IDD and compare their risk with that of the general population. METHODS: Using the TriNetX network, we identified patients with and without an IDD who had COVID-19. Subsequently, we compared the risk of developing any post-COVID-19 condition between these two groups, during the 90-180-day follow-up after SARS-CoV-2 infection. RESULTS: During the follow-up, patients with an IDD exhibited a significantly higher prevalence of post-COVID-19 conditions compared to the general population (hazard ratio [HR], 1.120; 95% confidence interval [CI]: 1.053-1.191). Specifically, COVID-19 survivors with IDD had a significantly increased risk of experiencing abnormal breathing (HR, 1.216; 95% CI: 1.077-1.373), abdominal symptoms (HR, 1.259; 95% CI: 1.128-1.406), fatigue (HR, 1.397; 95% CI: 1.216-1.606), anxiety/depression (HR, 1.157; 95% CI: 1.050-1.274), cognitive symptoms (HR, 1.828; 95% CI: 1.529-2.186), myalgia (HR, 1.325; 95% CI: 1.077-1.631), sleep disturbances (HR, 1.481; 95% CI: 1.148-1.910), and cough (HR, 1.315; 95% CI: 1.146-1.508) compared to the non-IDD group. CONCLUSIONS: Patients with IDD might be associated with a higher risk of post-COVID-19 conditions following SARS-CoV-2 infection compared to the general population.

Effectiveness of oral antiviral agents on long-term cardiovascular risk in nonhospitalized patients with COVID-19: A multicenter matched cohort study.

Although a novel oral antiviral agent can improve short-term COVID-19 outcomes, its effects on the long-term outcomes, namely the risk of major adverse cardiovascular events (MACEs), remains unknown. This retrospective cohort study used the TriNetX research network to identify nonhospitalized adult patients with COVID-19 between March 1, 2020, and January 1, 2022. A propensity score matching method was used to form two matched cohorts with and without receiving nirmatrelvir-ritonavir (NMV-r) or molnupiravir. The primary outcome was the incidence of MACEs within a 30-day to 1-year period following a diagnosis of COVID-19. Two cohorts of each 80 888 patients with balanced baseline characteristics were formed using propensity score matching. During the follow-up period, 976 patients in the study group and 1609 patients in the control group developed MACE. Overall, the study group had a significantly lower risk of MACE than the control group (hazard ratio [HR], 0.683; 95% confidence interval: 0.630-0.739). The significantly lower HRs of overall MACEs were consistently observed in most subgroup analyses (age: >41-≤64 years: 0.60 [0.52-0.89]; age: ≥65 years: 0.68 [0.62-0.76]; women: 0.63 [0.57-0.71]; men: 0.62 [0.55-0.70]; vaccinated: 0.74 [0.63-0.88]; unvaccinated: 0.66 [0.60-0.73]; NMV-r; 0.65 [0.59-0.71]; and molnupiravir: 0.75 [0.61-0.92]). In conclusion, novel oral antiviral agents, namely NMV-r and molnupiravir, were effective in reducing long-term MACEs among nonhospitalized patients with COVID-19, particularly when treated with NMV-r or in patients aged ≥40 years. These findings suggest the potential role of novel antiviral agents as a preventive measure to reduce further adverse cardiovascular outcomes.

Risk of cytomegalovirus diseases among coronavirus disease survivors: A retrospective cohort study.

This study was aimed at investigating the risk of cytomegalovirus (CMV) disease among coronavirus disease 2019 (COVID-19) survivors. In this retrospective cohort study, we used the TriNetX research network to identify adults with and without COVID-19 between January 1, 2022 and December 31, 2022. Propensity score matching was used to match the patients with and without COVID-19. The primary outcome was the risk of CMV disease during the 90-day follow-up period. Two matched cohorts comprising 2 501 634 patients with balanced baseline characteristics were created using propensity score matching. During the follow-up period, patients with COVID-19 had a higher risk of CMV disease than those without COVID-19 (hazard ratio [HR], 2.55; 95% confidence interval: 2.01-3.23). The higher risk of CMV disease in the COVID-19 cohort compared with that of the non-COVID-19 cohort remained unchanged in the subgroup analyses by sex (men: HR, 1.85 [1.38-2.47]; women: HR, 2.31 [1.63-3.27]), age (18-64 years: HR, 2.21 [1.71-2.85]; ≥65 years: HR, 1.97 [1.20-3.25]), obesity (HR, 1.54 [1.04-2.30]), diabetes mellitus (HR, 1.50 [1.08-2.08]), cancer (HR, 3.10 [1.95-4.92]), glucocorticoid use (HR, 3.14 [2.45-4.02]), transplantation (HR, 1.38 [1.08-1.77]), and unvaccinated status (HR, 2.37 [1.82-3.08]). In conclusion, COVID-19 can increase the risk of CMV disease. Clinicians should be aware of the risk of CMV disease in patients with COVID-19.

Clinical effectiveness of nirmatrelvir plus ritonavir in patients with COVID-19 and substance use disorders based on real-world data.

This study assessed the clinical efficacy of nirmatrelvir plus ritonavir (NMV-r) in treating patients with coronavirus disease-2019 (COVID-19) and substance use disorders (SUDs). This study included two cohorts: the first examined patients with SUDs, with and without a prescription for NMV-r, while the second compared patients prescribed with NMV-r, with and without a diagnosis of SUDs. SUDs were defined using ICD-10 codes, related to SUDs, including alcohol, cannabis, cocaine, opioid, and tobacco use disorders (TUD). Patients with underlying SUDs and COVID-19 were identified using the TriNetX network. We used 1:1 propensity score matching to create balanced groups. The primary outcome of interest was the composite outcome of all-cause hospitalization or death within 30 days. Propensity score matching yielded two matched groups of 10 601 patients each. The results showed that the use of NMV-r was associated with a lower risk of hospitalization or death, 30 days after COVID-19 diagnosis (hazard ratio (HR), 0.640; 95% confidence interval (CI): 0.543-0.754), as well as a lower risk of all-cause hospitalization (HR, 0.699; 95% CI: 0.592-0.826) and all-cause death (HR, 0.084; 95% CI: 0.026-0.273). However, patients with SUDs had a higher risk of hospitalized or death within 30 days of COVID-19 diagnosis than those without SUDs, even with the use of NMV-r (HR, 1.783; 95% CI: 1.399-2.271). The study also found that patients with SUDs had a higher prevalence of comorbidities and adverse socioeconomic determinants of health than those without SUDs. Subgroup analysis showed that the benefits of NMV-r were consistent across most subgroups with different characteristics, including age (patients aged ≥60 years [HR, 0.507; 95% CI: 0.402-0.640]), sex (women [HR, 0.636; 95% CI: 0.517-0.783] and men [HR, 0.480; 95% CI: 0.373-0.618]), vaccine status (vaccinated <2 doses [HR, 0.514; 95% CI: 0.435-0.608]), SUD subtypes (alcohol use disorder [HR, 0.711; 95% CI: 0.511- 0.988], TUD [HR, 0.666; 95% CI: 0.555-0.800]) and Omicron wave (HR, 0.624; 95% CI: 0.536-0.726). Our findings indicate that NMV-r could reduce all-cause hospitalization and death in the treatment of COVID-19 among patients with SUDs and support the use of NMV-r for treating patients with SUDs and COVID-19.

Efficacy of nirmatrelvir and ritonavir for post-acute COVID-19 sequelae beyond 3 months of SARS-CoV-2 infection.

The effect of nirmatrelvir plus ritonavir (NMV-r) on post-acute COVID-19 sequelae beyond 3 months of SARS-CoV-2 infection remains unknown. This retrospective cohort study utilized data from the TriNetX Research Network. We identified nonhospitalized adult patients with COVID-19 receiving a diagnosis between January 1 and July 31, 2022. Propensity score matching (PSM) was used to create two matched cohorts: NMV-r and non-NMV-r groups, respectively. We measured the primary outcomes using a composite of all-cause emergency room (ER) visits or hospitalization and a composite of post-COVID-19 symptoms according to the WHO Delphi consensus, which also stated that post COVID-19 condition occurs usually 3 months from the onset of COVID-19, during the follow-up period between 90 days after the index diagnosis of COVID-19 and the end of follow-up (180 days). Initially, we identified 12 247 patients that received NMV-r within 5 days of diagnosis and 465 135 that did not. After PSM, 12 245 patients remained in each group. During the follow-up period, patients treated with NMV-r had a lower risk of all-cause hospitalization and ER visits compared with untreated patients (659 vs. 955; odds ratio [OR], 0.672; 95% confidence interval [CI], 0.607-0.745; p < 0.0001). However, the overall risk of post-acute COVID-19 symptoms did not significantly differ between the two groups (2265 vs. 2187; OR, 1.043; 95% CI, 0.978-1.114; p = 0.2021). The reduced risk of all-cause ER visits or hospitalization in the NMV-r group and the similarities in the risk of post-acute COVID-19 symptoms between the two groups were consistent in the subgroups stratified by sex, age, and vaccination status. Early NMV-r treatment of nonhospitalized patients with COVID-19 was associated with reduced risk of hospitalization and ER visits during the period of 90-180 days after diagnosis compared with no NMV-r treatment; however, post-acute COVID-19 symptoms and mortality risk did not differ significantly between the groups.

Clinical effectiveness of oral antiviral agents in older patients with COVID-19 based on real-world data.

Several randomized controlled trials and real-world cohort studies have demonstrated the efficacies of nirmatrelvir plus ritonavir (NMV-r) and molnupiravir (MOV) in at-risk patients with COVID-19; however, the effectiveness of antisevere acute respiratory syndrome-coronavirus 2 treatments on older patients (≥65 years) remains unclear. This retrospective cohort study aimed to assess the clinical effectiveness of the oral antiviral agents, MOV and NMV-r, in older patients (≥65 years) infected with severe acute respiratory syndrome-coronavirus 2. Nonhospitalized older patients with COVID-19 between January 1, 2022, and December 31, 2022, were recruited from the TriNetX Research Network. Propensity score matching (PSM) was used to match patients who received either NMV-r or MOV treatment with those who did not receive any oral antiviral agents. Hazard ratios (HRs) for composite all-cause hospitalization or death during the 30-day follow-up period were calculated. PSM revealed two cohorts with 28 824 patients each having balanced baseline characteristics. The antiviral group was associated with significantly lower risk of the primary composite outcome of all-cause hospitalization or death than the control group (241 vs. 801; HR, 0.307; 95% confidence interval (CI), 0.27-0.36) during the follow-up period. For the secondary outcome, the antiviral group had a significantly lower risk of all-cause hospitalization (288 vs. 725; HR, 0.322; 95% CI, 0.28-0.37) and mortality (16 vs. 94; HR, 0.176; 95% CI, 0.10-0.30) than the control group. Moreover, the reduced risk of all-cause hospitalization or death remained consistent in patients receiving NMV-r (HR, 0.279; 95% CI, 0.24-0.33) and MOV (HR, 0.279; 95% CI, 0.21-0.38). Our results revealed that NMV-r and MOV decreased the all-cause hospitalization and death rates among older patients with COVID-19, supporting the use of antivirals in this vulnerable population.

Clinical efficacy of nirmatrelvir and ritonavir combination for treating diabetic patients with COVID-19.

The aim of this study was to investigate the clinical efficacy of a combination of nirmatrelvir and ritonavir (NMV-r) for treating COVID-19 in patients with diabetes mellitus (DM). This retrospective cohort study used the TriNetX research network to identify adult diabetic patients with COVID-19 between January 1, 2020, and December 31, 2022. Propensity score matching was used to match patients who received NMV-r (NMV-r group) with those who did not receive NMV-r (control group). The primary outcome was all-cause hospitalization or death during the 30-day follow-up period. Two cohorts comprising 13 822 patients with balanced baseline characteristics were created using propensity score matching. During the follow-up period, the NMV-r group had a lower risk of all-cause hospitalization or death than the control group (1.4% [n = 193] vs. 3.1% [n = 434]; hazard ratio [HR], 0.497; 95% confidence interval [CI], 0.420-0.589). Compared with the control group, the NMV-r group also had a lower risk of all-cause hospitalization (HR, 0.606; 95% CI, 0.508-0.723) and all-cause mortality (HR, 0.076; 95% CI, 0.033-0.175). This lower risk was consistently observed in almost all subgroup analyses, which examined sex (male: 0.520 [0.401-0.675]; female: 0.586 [0.465-0.739]), age (age 18-64 years: 0.767 [0.601-0.980]; ≥65 years: 0.394 [0.308-0.505]), level of HbA1c (<7.5%: 0.490 [0.401-0.599]; ≥7.5%: 0.655 [0.441-0.972]), unvaccinated (0.466 [0.362-0.599]), type 1 DM (0.453 [0.286-0.718]) and type 2 DM (0.430 [0.361-0.511]). NMV-r can help reduce the risk of all-cause hospitalization or death in nonhospitalized patients with DM and COVID-19.

Nutritional deficiency anemia and post-acute sequelae in patients with severe acute respiratory syndrome coronavirus 2 infection: A six-month retrospective cohort analysis of 30 892 patients.

The effect of anemia on the post-acute outcome of patients with severe acute respiratory syndrome coronavirus 2 infection was unclear. This study aimed to investigate the potential association between nutritional deficiency anemia (NDA) status and post-acute sequelae of patients with SARS-CoV-2 infection. This retrospective cohort study included patients with coronavirus disease (COVID-19) from January 1, 2022 to November 30, 2022 using the TriNetX research network. The patients were grouped into the NDA group comprising patients diagnosed with NDA and the control group comprising patients without NDA, and propensity score matching (PSM) was performed to balance the two groups. The primary outcome was a composite of post-COVID-19 condition, all-cause hospitalization, and all-cause death. The secondary outcomes were any individual outcomes of the primary composite. The follow-up period was set at 90-180 days after COVID-19 diagnosis. Two cohorts comprising 15 446 nonhospitalized patients with COVID-19 in each group with balanced baseline characteristics were created using PSM. During the follow-up period, the NDA group demonstrated a higher risk of the composite primary outcome, including post-COVID-19 condition, all-cause hospitalization, or all-cause death (hazard ratio [HR], 1.896; 95% confidence interval [CI] = 1.757-2.045). Regarding secondary outcomes, the NDA group was associated with worse outcomes, including post-COVID-19 condition (HR, 1.992; 95% CI = 1.403-2.828), all-cause hospitalization (HR, 1.856; 95% CI = 1.714-2.009), and all-cause death (HR, 3.922; 95% CI = 2.910-5.285) compared to the control group. Among nonhospitalized patients with COVID-19, NDA was associated with a higher risk of post-COVID-19 condition, all-cause hospitalization, and all-cause death during the 90-180-day follow-up period.

Efficacy and safety of adjunctive corticosteroids in the treatment of severe community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia (sCAP). METHODS: A comprehensive search was conducted using the Medline, Embase, ClinicalTrials.gov, and Scopus databases for articles published until April 24, 2023. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of adjunctive corticosteroids for treating sCAP were included. The primary outcome was the 30-day all-cause mortality. RESULTS: A total of severe RCTs involving 1689 patients were included in this study. Overall, the study group had a lower mortality rate at day 30 than the control group (risk ratio [RR], 0.61; 95% CI 0.44 to 0.85; p < 0.01) with low heterogeneity (I2 = 0%, p = 0.42). Compared to the control group, the study group had a lower risk of the requirement of mechanical ventilation (RR 0.57; 95% CI 0.45 to 0.73; p < 0.001), shorter length of intensive care unit (MD - 0.8; 95% CI - 1.4 to - 0.1; p = 0.02), and hospital stay (MD - 1.1; 95% CI - 2.0 to - 0.1; p = 0.04). Finally, no significant difference was observed between the study and the control groups in terms of gastrointestinal tract bleeding (RR 1.03; 95% CI 0.49 to 2.18; p = 0.93), healthcare-associated infection (RR 0.89; 95% CI 0.60 to 1.32; p = 0.56), and acute kidney injury (RR 0.68; 95% CI 0.21 to 2.26; p = 0.53). CONCLUSIONS: In patients with sCAP, adjunctive corticosteroids can provide survival benefits and improve clinical outcomes without increasing adverse events. However, because the pooled evidence remains inconclusive, further studies are required.

Real-world data analysis of post-COVID-19 condition risk in older patients.

This study investigated the risk of post-COVID-19 conditions in older patients with COVID-19 compared to those with influenza, and how age impacts this relationship. Patients aged ≥65 years with COVID-19 or influenza were identified using the TriNetX network. The risk of post-COVID-19 conditions was compared between survivors of COVID-19 and influenza, followed by a comparison of post-COVID-19 conditions risk between patients aged 65-74 years and those aged over 75 years. Compared with influenza survivors, post-COVID-19 conditions were significantly more prevalent in patients with COVID-19 (hazard ratio [HR], 1.534; 95% confidence interval [CI]: 1.405-1.675). Specifically, COVID-19 survivors have a significantly higher risk of experiencing abnormal breathing (HR, 2.052; 95% CI: 1.757-2.397), fatigue (HR, 1.587; 95% CI: 1.322-1.905), anxiety/depression (HR, 1.587; 95% CI: 1.322-1.905), cognitive symptoms (HR, 1.667; 95% CI: 1.295-2.146) and cough (HR, 1.250; 95% CI: 1.006-1.553) compared with the influenza group. Contrastingly, no significant difference was observed in the risk of any post-COVID-19 condition between COVID-19 survivors aged 65-74 years and those aged over 75 years (HR, 0.994; 95% CI: 0.920-1.073). However, a lower incidence of cognitive symptoms was observed in patients aged 65-74 years compared to those aged ≥75 years (HR, 0.543; 95% CI: 0.445-0.661). In conclusion, compared with influenza, older patients have a higher risk of developing post-COVID-19 conditions after SARS-CoV-2 infection, and those aged over ≥75 years may have an increased risk of developing cognitive symptoms compared to those aged 65-74 years.

Investigation of designated eye position and viewing zone for a two-view autostereoscopic display.

Designated eye position (DEP) and viewing zone (VZ) are important optical parameters for designing a two-view autostereoscopic display. Although much research has been done to date, little empirical evidence has been found to establish a direct relationship between design and measurement. More rigorous studies and verifications to investigate DEP and to ascertain the VZ criterion will be valuable. We propose evaluation metrics based on equivalent luminance (EL) and binocular luminance (BL) to figure out DEP and VZ for a two-view autostereoscopic display. Simulation and experimental results prove that our proposed evaluation metrics can be used to find the DEP and VZ accurately.

Clinical efficacy of nirmatrelvir plus ritonavir in patients with COVID-19 and preexisting cardiovascular diseases.

BACKGROUND: This study assessed the clinical efficacy of nirmatrelvir plus ritonavir (NMV-r) in treating patients with COVID-19 who have preexisting cardiovascular diseases (CVDs). METHODS: Patients with underlying CVDs and COVID-19 were included from the TriNetX network. We employed a 1:1 propensity score matching to create two comparable cohorts: patients receiving NMV-r and those not receiving NMV-r. The primary outcome was the composite outcome of all-cause hospitalization or death within 30 days. RESULTS: Propensity score matching yielded two matched cohorts of 10,847 patients each. The composite outcomes of all-cause hospitalization or death within 30 days were 2.2% (239 patients) in the NMV-r cohort and 4.7% (512 patients) in the control cohort, indicating reduced risk in the NMV-r cohort (hazard ratio [HR], 0.475; 95% confidence interval [CI], 0407-0.533). The NMV-r cohort exhibited lower risks of all-cause hospitalization (HR, 0.525; 95% CI, 0.449-0.615) and mortality (HR, 0.113; 95% CI, 0.052-0.246) compared with the control group. A similar trend was observed across most of the subgroups. CONCLUSIONS: Our findings indicate that NMV-r to treat COVID-19 could reduce all-cause hospitalization and death in patients with CVDs.

Clinical effectiveness of nirmatrelvir plus ritonavir for patients with COVID-19 and preexisting psychiatric disorders.

OBJECTIVES: This study assessed the clinical effectiveness of the combination of nirmatrelvir and ritonavir (NMV-r) in treating nonhospitalized patients with COVID-19 who have preexisting psychiatric disorders. METHODS: Patients diagnosed with COVID-19 and psychiatric disorders between 1 March 2020, and 1 December 2022, were included using the TriNetX network. The primary outcome was the composite outcome of all-cause emergency department (ED) visits, hospitalization, or death within 30 days. RESULTS: Propensity score matching yielded two cohorts of 20,633 patients each. The composite outcome of all-cause ED visits, hospitalization, or death within 30 days was 3.57% (737 patients) in the NMV-r cohort and 5.69% (1176) in the control cohort, resulting in a reduced risk in the NMV-r cohort (HR: 0.657; 95% confidence interval (CI): 0.599-0.720). The NMV-r cohort exhibited a lower risk of all-cause hospitalization (HR: 0.385; 95% CI: 0.328-0.451) and all-cause death (HR: 0.110; 95% CI: 0.053-0.228) compared with the control group. CONCLUSION: NMV-r could mitigate the risk of adverse outcomes in nonhospitalized patients with COVID-19 and preexisting psychiatric disorders. However, only a limited number of patients in this population received adequate treatment, thus emphasizing the importance of promoting its appropriate use.

Clinical efficacy of N-acetylcysteine for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Background: The association between N-acetylcysteine (NAC) and COVID-19 remains undetermined; therefore, this meta-analysis assessed the clinical efficacy of NAC in the treatment of patients with COVID-19. Methods: This study searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for studies published from their inception to December 17, 2022. Only randomized controlled trials (RCTs) that assessed the clinical efficacy of NAC for patients with COVID-19 were included. Results: Five RCTs involving 651 patients were included. There was no significant difference in mortality between the study group receiving NAC and the control group (15.6 % [50/320] vs. 32.3 %, [107/331]; risk ratio [RR]: 0.58; 95 % confidence interval [CI]: 0.24-1.40). In addition, the two groups did not differ with respect to the incidence of invasive mechanical ventilation (RR: 0.93; 95 % CI: 0.65-1.33), the risk of intensive care unit (ICU) admission (RR: 0.86; 95 % CI: 0.62-1.21), the length of hospital stay (mean difference [MD]: 0.17 days; 95 % CI: -0.67-1.01), and the length of ICU stay (MD: -0.77 days; 95 % CI: -2.97-1.42). Conclusions: The administration of NAC did not improve the clinical outcomes of patients with COVID-19; its routine use is not recommended for patients with SARS-CoV-2 infections.

The effectiveness of novel oral antiviral treatment for non-hospitalized high-risk patients with COVID-19 during predominance of omicron XBB subvariants.

OBJECTIVES: This study investigated the association between nirmatrelvir plus ritonavir (NMV-r) or molnupiravir and the outcomes of non-hospitalized high-risk patients with COVID-19 during Omicron XBB subvariants. METHODS: The retrospective cohort study used the TriNetX US collaborative network to identify non-hospitalized high-risk adult patients with COVID-19 between 1 February 2023, and 31 August 2023. Propensity score matching (PSM) was used to match patients receiving NMV-r or MOV (the study group) with those not receiving antivirals (the control group). RESULTS: Using PSM, two cohorts of 17,654 patients each with balanced baseline characteristics were identified. During the follow-up period, the study group had a lower risk of all-cause hospitalization, or death (3.2% [n = 564] versus 3.8% [n = 669]; HR, 0.796; 95% confidence interval [CI], 95% CI, 0.712-0.891). Compared with the control group, the study group had a significantly lower risk of all-cause hospitalization (3.1% vs. 3.4%; HR, 0.847; 95% CI, 0.754-0.950) and mortality (0.1% vs. 0.4%; HR, 0.295; 95% CI, 0.183-0.476). CONCLUSION: The use of novel oral antiviral including NMV-r or MOV can be associated with a lower risk of all-cause hospitalization, or death in non-hospitalized high-risk patients with COVID-19 during Omicron XBB wave.