Analysis of All-Cause Hospitalization and Death Among Nonhospitalized Patients With Type 2 Diabetes and SARS-CoV-2 Infection Treated With Molnupiravir or Nirmatrelvir-Ritonavir During the Omicron Wave in Hong Kong.

Importance: Diabetes and COVID-19 are both global pandemics, and type 2 diabetes is a common comorbidity in patients with acute COVID-19 and is proven to be a key determinant of COVID-19 prognosis. Molnupiravir and nirmatrelvir-ritonavir are oral antiviral medications recently approved for nonhospitalized patients with mild to moderate COVID-19, following demonstration of their efficacies in reducing adverse outcomes of the disease; it is crucial to clarify whether both oral antiviral medications are efficacious in a population consisting exclusively of patients with type 2 diabetes. Objective: To evaluate the effectiveness of molnupiravir and nirmatrelvir-ritonavir in a contemporary population-based cohort comprising exclusively nonhospitalized patients with type 2 diabetes and SARS-CoV-2 infection. Design, Setting, and Participants: This retrospective cohort study was performed using population-based electronic medical record data for patients in Hong Kong with type 2 diabetes and confirmed SARS-CoV-2 infection between February 26 and October 23, 2022. Each patient was followed up until death, outcome event, crossover of oral antiviral treatment, or end of the observational period (October 30, 2022), whichever came first. Outpatient oral antiviral users were divided into molnupiravir and nirmatrelvir-ritonavir treatment groups, respectively, and nontreated control participants were matched through 1:1 propensity score matching. Data analysis was performed on March 22, 2023. Exposures: Molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir-ritonavir (300 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days, or 150 mg nirmatrelvir and 100 mg ritonavir for patients with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m2). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and/or hospitalization. The secondary outcome was in-hospital disease progression. Hazard ratios (HRs) were estimated with Cox regression. Results: This study identified 22 098 patients with type 2 diabetes and COVID-19. A total of 3390 patients received molnupiravir and 2877 received nirmatrelvir-ritonavir in the community setting. After application of exclusion criteria followed by 1:1 propensity score matching, this study comprised 2 groups. One group included 921 molnupiravir users (487 men [52.9%]), with a mean (SD) age of 76.7 (10.8) years, and 921 control participants (482 men [52.3%]), with a mean (SD) age of 76.6 (11.7) years. The other group included 793 nirmatrelvir-ritonavir users (401 men [50.6%]), with a mean (SD) age of 71.7 (11.5) years, and 793 control participants (395 men [49.8%]), with a mean (SD) age of 71.9 (11.6) years. At a median follow-up of 102 days (IQR, 56-225 days), molnupiravir use was associated with a lower risk of all-cause mortality and/or hospitalization (HR, 0.71 [95% CI, 0.64-0.79]; P < .001) and in-hospital disease progression (HR, 0.49 [95% CI, 0.35-0.69]; P < .001) compared with nonuse. At a median follow-up of 85 days (IQR, 56-216 days), nirmatrelvir-ritonavir use was associated with a lower risk of all-cause mortality and/or hospitalization (HR, 0.71 [95% CI, 0.63-0.80]; P < .001) and a nonsignificantly lower risk of in-hospital disease progression (HR, 0.92 [95% CI, 0.59-1.44]; P = .73) compared with nonuse. Conclusions and Relevance: These findings suggest that both molnupiravir and nirmatrelvir-ritonavir oral antiviral medications were associated with a lower risk of all-cause mortality and hospitalization among patients with COVID-19 and type 2 diabetes. Further studies in specific populations, such as individuals in residential care homes and individuals with chronic kidney disease, are suggested.

Metformin Use in Relation to Clinical Outcomes and Hyperinflammatory Syndrome Among COVID-19 Patients With Type 2 Diabetes: A Propensity Score Analysis of a Territory-Wide Cohort

Aim This study was conducted in order to evaluate the association between metformin use and clinical outcomes in type 2 diabetes mellitus (T2DM) patients hospitalized with coronavirus disease 2019 (COVID-19). Methods Patients with T2DM with confirmed diagnosis of COVID-19 and admitted between January 21, 2020, and January 31, 2021 in Hong Kong were identified in our cohort. Exposure was defined as metformin use within 90 days prior to admission until hospital discharge for COVID-19. Primary outcome was defined as clinical improvement of ≥1 point on the WHO Clinical Progression Scale (CPS). Other outcomes were hospital discharge, recovery, in-hospital death, acidosis, hyperinflammatory syndrome, length of hospitalization, and changes in WHO CPS score. Results Metformin use was associated with greater odds of clinical improvement (OR = 2.74, p = 0.009), hospital discharge (OR = 2.26, p = 0.009), and recovery (OR = 2.54, p = 0.005), in addition to lower odds of hyperinflammatory syndrome (OR = 0.71, p = 0.021) and death (OR = 0.41, p = 0.010) than control. Patients on metformin treatment had a shorter hospital stay (−2.76 days, p = 0.017) than their control counterparts. The average WHO CPS scores were significantly lower in metformin users than non-users since day 15 (p < 0.001). However, metformin use was associated with higher odds of acidosis. Conclusions Metformin use was associated with lower mortality and lower odds for hyperinflammatory syndrome. This provides additional insights into the potential mechanisms of the benefits of metformin use in T2DM patients with COVID-19.

Use of DPP4i reduced odds of clinical deterioration and hyperinflammatory syndrome in COVID-19 patients with type 2 diabetes: Propensity score analysis of a territory-wide cohort in Hong Kong.

BACKGROUND AND OBJECTIVES: Type 2 diabetes mellitus (T2DM) patients with Coronavirus Disease 2019 (COVID-19) have poorer prognosis. Inconclusive evidence suggested dipeptidyl peptidase-4 inhibitors (DPP4i) might reduce inflammation and prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry, hence further evaluation on DPP4i is needed. METHODS: 1214 Patients with T2DM were admitted with COVID-19 between 21st January 2020 and 31st January 2021 in Hong Kong. Exposure was DPP4i use within the 90 days prior to admission for COVID-19. Assessed outcomes included clinical deterioration, clinical improvement, low viral load, positive Immunoglobulin G (IgG) antibody, hyperinflammatory syndrome, proportion of IgG antibody, clinical status and length of hospitalization. Multivariable logistic and linear regression models were performed to estimate odds ratios (OR) and their 95% confidence intervals (CI) of event outcomes and continuous outcomes, respectively. RESULTS: DPP4i users (N = 107) was associated with lower odds of clinical deterioration (OR=0.71, 95%CI 0.54 to 0.93, P = 0.013), hyperinflammatory syndrome (OR=0.56, 95%CI 0.45 to 0.69, P < 0.001), invasive mechanical ventilation (OR=0.30, 95%CI 0.21 to 0.42, P < 0.001), reduced length of hospitalization (-4.82 days, 95%CI -6.80 to -2.84, P < 0.001), proportion of positive IgG antibody on day-3 (13% vs 8%, p = 0.007) and day-7 (41% vs 26%, P < 0.001), despite lack of association between DPP4i use and in-hospital mortality. CONCLUSION: DPP4i use was associated with reduced odds of clinical deterioration and hyperinflammatory syndrome. Prospective studies are warranted to elucidate the role of DPP4i in T2DM and COVID-19.

Insights From Prospective Follow-up of Thyroid Function and Autoimmunity Among Covid-19 Survivors

Objective: Occurrence of Graves’ disease and Hashimoto’s thyroiditis after coronavirus disease 2019 (COVID-19) raised the concern about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggering thyroid autoimmunity. Uncertainties remain regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. We carried out a prospective study to characterize the evolution of thyroid function and autoimmunity among COVID-19 survivors. Method: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for confirmed COVID-19 from 21 July to 21 September 2020 were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and anti-thyroid antibodies were measured on admission and at 3 months. Positive anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) was defined by &gt;100 units. Results: Among 200 COVID-19 survivors, 122 had reassessment thyroid function tests (TFTs) (median age: 57.5 years;49.2% men). Baseline characteristics of patients who did and did not have reassessment were comparable. Among the 20 patients with baseline abnormal TFTs on admission, mostly low fT3, 15 recovered. Of the 102 patients with normal TFTs on admission, two (2.0%) had new onset abnormal TFTs, which may represent TFTs in different phases of thyroiditis (one had mildly elevated TSH 5.8 mIU/L, with normal fT4 [16 pmol/L] and fT3 [4.3 pmol/L], the other had mildly raised fT4 25 pmol/L with normal TSH [1.1 mIU/L] and fT3 [4.7 pmol/L]). Among 104 patients with anti-thyroid antibody titers reassessed, we observed increases in anti-TPO (baseline: 28.3 units [IQR 14.0-67.4] vs reassessment: 35.0 units [IQR: 18.8-99.0];p&lt;0.001) and anti-Tg titers (baseline: 6.6 units [IQR 4.9-15.6] vs reassessment: 8.7 units [IQR: 6.6-15.4];p&lt;0.001), but no change in anti-TSHR titer (baseline: 1.0 IU/L [IQR: 0.8-1.2] vs reassessment: 1.0 IU/L [IQR: 0.8-1.3];p=0.486). Of the 82 patients with negative anti-TPO at baseline, 16 had significant interval increase in anti-TPO titer by &gt;12 units (2×6 [precision of the anti-TPO assay in normal range being 6 units per SD]), of these, four became anti-TPO positive. Factors associated a significant increase in anti-TPO titer included worse baseline clinical severity (p=0.018), elevated C-reactive protein during hospitalization (p=0.033), and higher baseline anti-TPO titer (p=0.005). Conclusion: Majority of thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis could occur during convalescence, though uncommon. Importantly, we provided the novel observation of an increase in anti-thyroid antibody titers post-COVID-19, suggesting the potential of SARS-CoV-2 in triggering thyroid autoimmunity, which warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.