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.

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.

The clinical efficacy of melatonin in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

Background: The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide, with cytokine storm leading to exaggerating immune response, multi-organ dysfunction and death. Melatonin has been shown to have anti-inflammatory and immunomodulatory effects and its effect on COVID-19 clinical outcomes is controversial. This study aimed to conduct a meta-analysis to evaluate the impact of melatonin on COVID-19 patients. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched without any language or publication year limitations from inception to 15 Nov 2022. Randomized controlled trials (RCTs) using melatonin as therapy in COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included were the recovery rate of clinical symptoms, changes in the inflammatory markers like C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR). A random-effects model was applied for meta-analyses, and further subgroup and sensitivity analyses were also conducted. Results: A total of nine RCTs with 718 subjects were included. Five studies using melatonin with the primary outcome were analyzed, and the pooled results showed no significant difference in mortality between melatonin and control groups with high heterogeneity across studies identified (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.47-1.11, p = 0.14, I2 = 82%). However, subgroup analyses revealed statistically significant effects in patients aged under 55 years (RR 0.71, 95% CI 0.62-0.82, p < 0.01) and in patients treated for more than 10 days (RR 0.07, 95% CI 0.01-0.53, p = 0.01). The recovery rate of clinical symptoms and changes in CRP, ESR, and NLR were not statistically significant. No serious adverse effects were reported from melatonin use. Conclusion: In conclusion, based on low certainty of evidence, the study concluded that melatonin therapy does not significantly reduce mortality in COVID-19 patients, but there are possible benefits in patients under 55 years or treated for more than 10 days. With a very low certainty of evidence, we found no significant difference in the recovery rate of COVID-19 related symptoms or inflammatory markers in current studies. Further studies with larger sample sizes are warranted to determine the possible efficacy of melatonin on COVID-19 patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022351424.

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.

Long-term risk of herpes zoster following COVID-19: A retrospective cohort study of 2 442 686 patients.

The long-term risk of herpes zoster (HZ) after recovery from a SARS-CoV-2 infection is unclear. This retrospective cohort study assessed the risk of HZ in patients following a COVID-19 diagnosis. This retrospective, propensity score-matched cohort study was based on the multi-institutional research network TriNetX. The risk of incident HZ in patients with COVID-19 was compared with that of those not infected with SARS-CoV-2 during a 1-year follow-up period. Hazard ratios (HRs) and 95% confidence intervals (CIs) of HZ and its subtypes were calculated. This study identified 1 221 343 patients with and without COVID-19 diagnoses with matched baseline characteristics. During the 1-year follow-up period, patients with COVID-19 had a higher risk of HZ compared with those without COVID-19 (HR: 1.59; 95% CI: 1.49-1.69). In addition, compared with the control group patients, those with COVID-19 had a higher risk of HZ ophthalmicus (HR: 1.31; 95% CI: 1.01-1.71), disseminated zoster (HR: 2.80; 95% CI: 1.37-5.74), zoster with other complications (HR: 1.46; 95% CI: 1.18-1.79), and zoster without complications (HR: 1.66; 95% CI: 1.55-1.77). Kaplan-Meier curve analysis (log-rank p < 0.05) results indicated that the risk of HZ remained significantly higher in patients with COVID-19 compared with those without COVID-19. Finally, the higher risk of HZ in the COVID-19 cohort compared with that in the non-COVID-19 cohort remained consistent across subgroup analyses regardless of vaccine status, age, or sex. The risk of HZ within a 12-month follow-up period was significantly higher in patients who had recovered from COVID-19 compared with that in the control group. This result highlights the importance of carefully monitoring HZ in this population and suggests the potential benefit of the HZ vaccine for patients with COVID-19.

Clinical efficacy of probiotics in the treatment of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study was conducted to assess the clinical efficacy of probiotics in the treatment of patients with COVID19. METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for studies from their inception to 8 February 2022. Randomized controlled trials (RCTs) that compared the clinical efficacy of probiotics with usual care or standard care for patients with COVID19 were included. The primary outcome was all-cause mortality. Random-effects model using MantelHaenszel and inverse variance methods were performed to analyze the data. RESULTS: Eight RCTs with 900 patients were included. The study group receiving probiotics had a non-significantly lower rate of mortality than the control group had, but this difference was not significant (risk ratio [RR], 0.51; 95% CI, 0.22 to 1.16). However, the study group had significantly lower rates of dyspnea (RR, 0.11; 95% CI, 0.02 to 0.60), fever (RR, 0.37; 95% CI, 0.16 to 0.85) and headache (RR, 0.19; 95% CI, 0.05 to 0.65). Higher complete remission of COVID-19-associated symptoms was observed in the study group than the control group (RR, 1.89; 95% CI, 1.40-2.55). CONCLUSIONS: Although probiotics use did not improve clinical outcomes or reduce inflammatory markers, it may relieve COVID-19-associated symptoms.

Clinical efficacy and safety of molnupiravir for nonhospitalized and hospitalized patients with COVID-19: A systematic review and meta-analysis of randomized control trials.

The efficacy of molnupiravir in treating patients with coronavirus disease 2019 (COVID-19) has been inconsistent across randomized controlled trials (RCTs). Thus, this meta-analysis was conducted to clarify the literature. A literature search of electronic databases-PubMed, Embase, and Cochrane Library-was performed to identify relevant articles published up to December 31, 2022. Only RCTs that investigated the clinical efficacy and safety of molnupiravir for patients with COVID-19 were included. The primary outcome was all-cause mortality at 28-30 days. This pooled analysis of nine RCTs did not reveal a significant difference in all-cause mortality between molnupiravir and control groups (risk ratio [RR], 0.43; 95% confidence interval [CI], 0.10-1.77) for overall patients. However, the risks of mortality and hospitalization were lower in the molnupiravir group than in the control group (mortality: RR, 0.28; 95% CI, 0.10-0.79; hospitalization: RR, 0.67; 95% CI, 0.45-0.99) among nonhospitalized patients. In addition, molnupiravir use was associated with a borderline higher virological eradication rate relative to the control (RR, 1.05; 95% CI, 1.00-1.11). Finally, no significant difference in adverse event risk was discovered between the groups (RR, 0.98; 95% CI, 0.89-1.08). The findings reveal the clinical benefits of molnupiravir for nonhospitalized patients with COVID-19. However, molnupiravir may not improve the clinical outcomes of hospitalized patients. These findings support the recommended use of molnupiravir for treating nonhospitalized patients with COVID-19 but not for hospitalized patients.