COVID-19 Outpatients Research Articles

Real-world analysis of safety, tolerability, and adherence to nirmatrelvir-ritonavir (paxlovid) in primary care COVID-19 outpatients.

This retrospective cross-sectional study aims to evaluate the safety, tolerability, and adherence of patients prescribed Nirmatrelvir-ritonavir (Paxlovid) in outpatient settings, focusing on its use in managing category 2 COVID-19 patients across three primary healthcare clinics in Selangor, Malaysia. Data were collected from the Paxlovid pharmacy registry and medical records at Klinik Kesihatan Seksyen 7, Klinik Kesihatan Seksyen 19, and Klinik Kesihatan Kelana Jaya between April 1, 2022, and November 30, 2022. This study analysed data from 415 category 2 COVID-19 patients aged ≥ 18years. The primary and secondary outcomes included the assessment of patient demographics, Paxlovid dosing, current medication, changes in drug regimen, adherence, and adverse drug reactions (ADR). Pharmacists follow-ups were conducted on days 3 and 5 post-medication initiation. The majority (79.5%) of the cohort experienced ADR, predominantly dysgeusia, diarrhoea, body ache, vomiting, and nausea. Despite this, the ADRs were generally well-tolerated, with no severe impacts reported. High adherence was observed, with 96.9% of patients completing the 5-day regimen. The primary reasons for non-adherence included adverse effect intolerability, dosing ambiguity, forgetfulness, concerns about ADR, and perceived health improvement. Notable medications interacting with Paxlovid were simvastatin, amlodipine, and atorvastatin, and 21.7% of 23 concurrent medications were found not to comply with the recommended interventions by the University of Liverpool COVID-19 Drug Interaction database. Paxlovid demonstrates a high level of safety and tolerability in outpatient COVID-19 patients, with optimal adherence observed. This study underscores the vital role of healthcare professionals in managing Paxlovid within primary healthcare and highlights the need for broader research and direct patient involvement to enhance treatment strategies against COVID-19.

Real-world effectiveness of early anti-SARS therapy in severely immunocompromised COVID-19 outpatients during the SARS-CoV-2 omicron variant era: a propensity score-adjusted retrospective cohort study.

The effectiveness of the early treatment for antiviral agents in SARS-CoV-2 infection is closely related to patient comorbidities. Data on effectiveness in immunocompromised patients are limited, with reports involving highly heterogeneous and not well-defined populations. We aimed to assess the effectiveness of treatment in reducing hospitalizations in a real-world cohort of severely immunocompromised COVID-19 outpatients. We conducted a multicentre, retrospective, observational cohort study of immunocompromised outpatients attended in infectious diseases departments from 1 January to 31 December 2022. Propensity score matching (PSM) multivariable logistic regression models were used to estimate the adjusted odds ratio [(aOR, 95% confidence interval (CI)] for the association between antiviral prescription and outcome (COVID-19-related hospitalization up to Day 90). We identified 746 immunocompromised outpatients with confirmed SARS-CoV-2 infection. After eligibility criteria and PSM, a total of 410 patients were analysed: 205 receiving treatment (remdesivir, sotrovimab or nirmatrelvir/ritonavir) and 205 matched controls. Fifty-two patients required at least one COVID-19-related hospitalization 8 (3.9%) versus 44 (21.5%) in the antiviral and matched control cohorts, respectively. There were 13 deaths at 90 days, of which only 4 were COVID-19-related and none in the antiviral treatment group. After adjustment for residual confounders, the use of early therapy was associated with a protective effect on the risk of hospitalization [aOR 0.13 (0.05-0.29)], as was the use of biological immunomodulators [aOR 0.27 (0.10-0.74)], whereas chronic obstructive pulmonary disease [aOR 4.65 (1.09-19.69)] and anti-CD20 use [aOR 2.76 (1.31-5.81)] increased the odds. Early antiviral treatment was associated with a reduced risk of COVID-19-related hospitalization in ambulatory severely immunocompromised COVID-19 patients.

Individual use of self-medication and other remedies in COVID-19 outpatients in Western-Pomerania

We analyzed data from positively tested COVID-19 outpatients to describe self-medication with OTC drugs and use of other remedies against symptoms of SARS-CoV-2 infection. We specifically considered their type and frequency, as well as associations with patient characteristics, and reasons for use. Data were collected between May 1, 2020 and February 22, 2021 with two questionnaires in an observational cohort study with PCR-confirmed SARS-CoV-2-positive adult outpatients in the district of Western Pomerania in Germany. 523 out of 710 outpatients (74%; 340 women and 183 men) reported using drugs and other remedies to relieve COVID-19-symptoms. Overall, participants reported utilization of 1282 finished dosage products or remedies, including 213 different ingredients. In the population of 710 outpatients, utilization of ibuprofen (26%), acetaminophen (21%), metamizole (14%), and acetylsalicylic acid (10%) was most commonly reported. Phytopharmaceuticals, herbal and animal products as well as vitamins and minerals were also frequently reported. Among the 523 participants who used drugs and other remedies, most commonly mentioned reasons for use were headache (40%), other kinds of pain (e.g. myalgia; 37%), fever (24%) and cough (16%). Our analysis showed that a majority of the participants tried to alleviate COVID-19-symptoms using drugs and other remedies. Especially analgesic and antipyretic agents, followed by herbal medicines, were used very frequently.Trial registration: German Register for Clinical Studies DRKS00021672, first registration on December 1st, 2020.

COVID-19, Nutrients and Lifestyle Eating Behaviors: A Narrative Review.

COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), quickly emerged as the most significant event of the new millennium. A balanced diet seems to ensure the proper functioning of the immune system and plays a fundamental role in the prevention of viral disease, inflammation, or thrombosis. The principal aim of this secondary study was to investigate the relationship between nutrients, lifestyle eating behaviors, and SARS-CoV-2 infection. A narrative review was conducted in the PubMed-Medline database, analyzing primary studies. Our review identified 21 relevant studies: 13 focused on vitamins, 1 on omega-3 supplementation, 1 on probiotics, and 6 on lifestyle and dietary behaviors. Vitamin supplementation has shown promise in attenuating COVID-19 symptoms and reducing mortality risk. Specifically, vitamin D has demonstrated efficacy in enhancing immune responses among patients with the disease. While preliminary evidence suggests the potential benefits of omega-3 and probiotic supplementation in improving health outcomes for COVID-19 outpatients, further research is needed to solidify these findings. The lifestyle changes imposed by lockdown measures have adversely affected psychological well-being and exacerbated health issues associated with reduced physical activity and poor dietary habits.

Real-world evaluation of early remdesivir in high-risk COVID-19 outpatients during Omicron including BQ.1/BQ.1.1/XBB.1.5

BackgroundA trial performed among unvaccinated, high-risk outpatients with COVID-19 during the delta period showed remdesivir reduced hospitalization. We used our real-world data platform to determine the effectiveness of remdesivir on reducing 28-day hospitalization among outpatients with mild-moderate COVID-19 during an Omicron period including BQ.1/BQ.1.1/XBB.1.5.MethodsWe did a propensity-matched, retrospective cohort study of non-hospitalized adults with SARS-CoV-2 infection between April 7, 2022, and February 7, 2023. Electronic healthcare record data from a large health system in Colorado were linked to statewide vaccination and mortality data. We included patients with a positive SARS-CoV-2 test or outpatient remdesivir administration. Exclusion criteria were other SARS-CoV-2 treatments or positive SARS-CoV-2 test more than seven days before remdesivir. The primary outcome was all-cause hospitalization up to day 28. Secondary outcomes included 28-day COVID-related hospitalization and 28-day all-cause mortality.ResultsAmong 29,270 patients with SARS-CoV-2 infection, 1,252 remdesivir-treated patients were matched to 2,499 untreated patients. Remdesivir was associated with lower 28-day all-cause hospitalization (1.3% vs. 3.3%, adjusted hazard ratio (aHR) 0.39 [95% CI 0.23–0.67], p < 0.001) than no treatment. All-cause mortality at 28 days was numerically lower among remdesivir-treated patients (0.1% vs. 0.4%; aOR 0.32 [95% CI 0.03–1.40]). Similar benefit of RDV treatment on 28-day all-cause hospitalization was observed across Omicron periods, aOR (95% CI): BA.2/BA2.12.1 (0.77[0.19–2.41]), BA.4/5 (0.50[95% CI 0.50–1.01]), BQ.1/BQ.1.1/XBB.1.5 (0.21[95% CI 0.08–0.57].ConclusionAmong outpatients with SARS-CoV-2 during recent Omicron surges, remdesivir was associated with lower hospitalization than no treatment, supporting current National Institutes of Health Guidelines.

Colchicine-The Divine Medicine against COVID-19.

Colchicine has a number of effects that suggest it may be useful in the treatment of COVID-19. Myeloid cells are a major source of dysregulated inflammation in COVID-19. The hyperactivation of the NLRP3 inflammasome and the subsequent cytokine storm take place precisely inside them and can lead to multiorgan damage and death. NLRP3 inflammasome inhibition has been assessed at micromolar colchicine concentrations which cannot be achieved in serum. However, colchicine has remarkable ability to accumulate intensively in leukocytes, where the cytokine storm is generated. Over 50 observational studies and randomized clinical trials, small randomized non-controlled trials, and retrospective cohort studies were initiated to test its healing effect in vivo, leading to conflicting, rather disappointing results. The WHO gives a "Strong recommendation against" the use of colchicine for COVID-19 treatment. This is because low doses of colchicine are always used, where the concentrations required to inhibit the NLRP3 inflammasome in leukocytes cannot be reached. Considering this, from March 2020, we started the administration of higher doses of colchicine. Our assumption was that a safe increase in colchicine doses to reach micromolar concentrations in leukocytes will result in NLRP3 inflammasome/cytokine storm inhibition. We demonstrated that in 785 inpatients treated with increasing doses of colchicine, mortality fell between two and seven times. Our data, including a large number of COVID-19 outpatients, showed that nearly 100% of the patients treated with this therapeutic regimen escaped hospitalization. In addition, post-COVID-19 symptoms in those treated with colchicine were significantly rarer. As a large number of viruses can overactivate the NLRP3 inflammasome (like seasonal influenza), we are convinced that higher colchicine doses would be useful in these cases as well.

Rates of Vaccination against COVID-19 in Psychiatric Outpatients.

The aim of this study was to compare the rates of vaccination against COVID-19 infection in psychiatric outpatients and the general population, as well as rates of infected patients. In addition, the level and type of anxiety due to the pandemic were observed in patients with psychotic, anxiety, and depressive disorders. In the present study, 171 patients with pre-existing mental disorders completed the questionnaire about the doses and types of vaccination against COVID-19. During 2021-2023, patients with different mental disorders, aged from 18 to 80, were included. All patients filled in a self-reported questionnaire including general information (age, sex, marriage, education, working status, comorbid conditions) as well as questions about mental health, receiving vaccination, and the course of COVID-19 infection if it was present. All patients gave informed consent for the interview. Patients with pre-existing mental disorders were more likely to be vaccinated against COVID-19 compared with the general population. The Sinopharm vaccine was most frequently applied. In the observed patients, 46.8% were infected, but just 7% had a medium or serious form of infection and were not vaccinated. In our study, the percentage of vaccinated psychiatric patients was greater than that in the general population, except in psychotic patients, who were mostly limited by fear. Such results can be explained by the high percentage of somatic comorbidities in this population and perhaps insufficient information about the positive effects of vaccination.

Long-term course of ambulatory patients with COVID-19 initially treated with enoxaparin vs no anticoagulation: final analysis of the OVID (enoxaparin for outpatients with COVID-19) randomized trial

BackgroundEarly thromboprophylaxis does not prevent hospital admissions and death among outpatients with symptomatic COVID-19. Its impact on long-term outcomes, including long COVID symptoms and performance status, is unknown. ObjectivesTo assess the long-term effects of thromboprophylaxis given at the time of acute COVID-19 in outpatients. MethodsThe OVID (enoxaparin for outpatients with COVID-19) trial randomized outpatients older than 50 years with acute COVID-19 to receive either subcutaneous enoxaparin 40 mg once daily for 14 days or standard of care (no thromboprophylaxis). In this follow-up study, we assessed the 2-year outcomes, including all-cause hospitalization and death, cardiovascular events, long COVID symptoms, and functional limitations based on the Post–COVID-19 Functional Status (PCFS) scale and EuroQol-5 Dimensions-5 Levels scale. ResultsOf 469 potentially eligible patients, 468 survived, of whom 439 (mean age 59 years; 54% men) participated in the Post-OVID study. There was no difference in terms of hospitalization and death (8.3% in the treatment group vs 10% in controls; relative risk, 0.83; 95% CI, 0.5-1.5) and of cardiovascular events between groups. The risk of presenting with long COVID symptoms was similar in the 2 groups (44% in the treatment group vs 47% in the standard of care group), with no difference between groups also concerning individual symptoms. A PCFS grade of 1 to 3, indicating light-to-moderate functional limitation, was recorded in 15% of patients in each group (odds ratio, 0.98; 95% CI, 0.6-1.7). No patients reported severe limitations (PCFS grade 4). Median EuroQol visual analog scale score was 85 on 100 points (IQR, 80-90 for the standard of care group and 75-90 for the enoxaparin group). ConclusionEarly thromboprophylaxis does not improve long-term, 2-year clinical and functional outcomes among symptomatic ambulatory patients with acute COVID-19.

Unveiling therapeutic dynamics: An in-depth comparative analysis of neutralizing monoclonal antibodies and favipiravir in alleviating COVID-19 outpatients impacts among middle-aged and special populations (MA-FAST)

BackgroundNeutralizing monoclonal antibodies (NMabs) are recognized for their efficacy against non-severe COVID-19. However, spike protein mutations may confer resistance. This study evaluates the effectiveness of favipiravir (FPV) versus NMabs in preventing severe COVID-19 in special populations. MethodsA retrospective cohort was conducted on middle-aged, elderly, diabetic, or obese patients with COVID-19 treated with either FPV or NMabs. Propensity score matching (PSM) was used for analysis. ResultsThe study included 1410 patients, resulting in four cohorts: middle-aged (36), elderly (48), diabetic (46), and obese (28) post-PSM. No significant differences were noted in 28-day emergency department (ED) visits across all groups between NMabs and FPV treatments, despite lower immunity in the FPV group. However, the diabetic group treated with FPV had higher 28-day hospitalization and oxygen supplemental, with no differences in the other groups. Intensive care unit (ICU) admissions, invasive mechanical ventilation, and mortality rates were similar between the two treatments. ConclusionsEarly dose-adjusted FPV showed no difference from NMabs in preventing ED visits, ICU admissions, ventilator needs, or mortality among patients with major comorbidities. Diabetic patients on FPV experienced higher hospitalizations and oxygen needs, with no observed differences in other groups. FPV may be a viable alternative, especially in settings with limited resources.

Symptom Clusters in Acute SARS-CoV-2 Infection and Long COVID Fatigue in Male and Female Outpatients.

(1) Background: After an acute SARS-CoV-2 infection, patients are at risk of developing Long COVID, with fatigue as a frequent and serious health problem. Objectives: To identify symptom clusters in acute SARS-CoV-2 infections and investigate their associations with the development of Long COVID fatigue, and to examine sex-specific differences. (2) Methods: The analysis included a total of 450 COVID-19 outpatients, of whom 54.4% were female. The median ages of the men and women were 51 years (IQR 36.0; 60.0) and 48 years (IQR 33.0; 57.0), respectively. Data collection took place between November 2020 and May 2021, with a median time between acute SARS-CoV-2 infection and examination in the study center of 240 days (IQR 133; 326). The Fatigue Assessment Scale (FAS) was used to identify fatigue and its severity. A multiple correspondence analysis was used to group forty-two COVID-19 symptoms into seven symptom clusters. Logistic and log-linear regressions were used to investigate associations between acute symptom clusters and Long COVID fatigue as dichotomous and continuous outcome, respectively. (3) Results: Fatigue occurred more frequently in women than in men (45% vs. 25%) and the median FAS score, indicating severity of fatigue, was higher in women than in men. The comparison between men and women revealed notable differences in four out of seven clusters. The strongest associations between symptom clusters in infection and Long COVID fatigue were identified for the cluster "cognitive and mental symptoms". In the log-linear regression model, each additional symptom in this cluster was associated with an increase of the FAS score by 5.13% (95% CI: [0.04; 0.07]; p < 0.001). The results of the logistic regression models supported this finding. Each additional symptom in this symptom cluster increased the odds of fatigue by 42% (95% CI: [1.23; 1.66]; p < 0.001). (4) Conclusions: In our study in COVID-19 outpatients, a strong association was observed between the number of symptoms in the cluster "cognitive and mental symptoms" during acute SARS-CoV-2 infection and the risk of developing fatigue months later. The consequent use of preventive and therapeutic strategies is necessary to decrease the burden of fatigue in the context of Long COVID.

Vital Signs as Predictors of Oxygen Requirements in COVID-19 Outpatients: The Development of a Streamlined Risk Score.

With COVID-19 becoming a common disease, primary care facilities such as clinics are required to efficiently triage patients at high risk of severe illness within the constraints of limited medical resources. However, existing COVID-19 severity risk scores require detailed medical history assessments, such as evaluating the severity of pneumonia via chest CT and accounting for past and comorbid conditions. Therefore, they may not be suitable for practical use in clinical settings with limited medical resources, including personnel and equipment. The goal is to identify key variables that predict the need for oxygen therapy in COVID-19 patients and develop a simplified clinical risk score based solely on vital signs to predict oxygen requirements. A retrospective observational study of 584 outpatients with COVID-19 confirmed by polymerase chain reaction test visited Sasebo Chuo Hospital between April 28, 2022, and August 18, 2022. Analyses were conducted after adjustment for background factors of age and sex with propensity score matching. We used the Fisher test for nominal variables and the Kruskal-Wallis test for continuous variables. After adjusting for age and sex, several factors significantly correlated with the need for oxygen within seven days including body temperature (p < 0.001), respiratory rate (p = 0.007), SpO2 (p < 0.001), and the detection of pneumonia on CT scans (p = 0.032). The area under the receiver-operating characteristic curve for the risk score based on these vital signs and CT was 0.947 (95% confidence interval: 0.911-0.982). The risk score based solely on vital signs was 0.937 (0.900-0.974), demonstrating the ability to predict oxygen administration with no significant differences. Body temperature, advanced age, increased respiratory rate, decreased SpO2, and the presence of pneumonia on CT scans were significant predictors of oxygen need within seven days among the study participants. The risk score, based solely on vital signs, effectively and simply assesses the likelihood of requiring oxygen therapy within seven days with high accuracy. The risk score, which utilizes only age and vital signs and does not require a detailed patient history or CT scans, could streamline hospital referral processes for admissions.

Telemedical management of symptomatic COVID-19 outpatients.

COVID-19 remains a challenge to individual health and healthcare resources worldwide. Telemedical surveillance might minimise hospitalisation and direct patient-physician contacts. Yet, randomised clinical trials evaluating telemedical management of COVID-19 patients are lacking. COVID-SMART is a randomised, open-label, controlled clinical trial investigating whether telemedicine reduces the primary end-point of hospitalisation or any unscheduled utilisation of an emergency medical service within 30 days of follow-up. Key secondary end-points included mortality and primary end-point components. We enrolled acutely infected SARS-CoV-2 patients suitable for outpatient care. All presented with ≥1 risk factor for an adverse COVID-19 course. Patients were randomised 1:1 into a control group receiving standard of care and an intervention group receiving smartphone-based assessment of oxygen saturation, heart rate and electrocardiogram, and telemedical counselling via a 24/7 emergency hotline. Of 607 enrolled patients (mean±sd age 46.7±13.5 years), 304 were randomised into the intervention and 303 into the control group. The primary end-point occurred in 6.9% (n=21) of the intervention and in 9.6% (n=29) of the control group (hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.41-1.26; p=0.24). No deaths occurred during follow-up. Fewer intervention group participants utilised outpatient-based emergency medical services (HR 0.43, 95% CI 0.20-0.90; p=0.03). COVID-SMART is the first randomised clinical trial assessing the benefit of telemedicine in an acute respiratory infectious disease. Whereas telemedical management did not reduce the primary end-point of hospitalisation, fewer intervention group patients used outpatient-based emergency services, suggesting a potential benefit for less-acutely infected individuals.

Physicians’ irrational attitudes on the antibiotic prescribing for the treatment of COVID-19 in Turkey: A multicenter survey

BackgroundThe inappropriate and excessive use of antibiotics during the coronavirus pandemic has become an important issue.ObjectiveOur primary aim is to ascertain the attitudes of physicians toward the antibiotics prescribing for the treatment of COVID-19 in Turkey. Our secondary aim was to identify factors affecting to physicians’ decisions regarding antibiotic therapy for the treatment of COVID-19 and risk factors associated with antibiotic overprescribing.MethodsIt was a multicenter cross-sectional survey. Physicians from 63 different cities were invited to survey through social media (Facebook, Instagram, WhatsApp). Data were collected from respondents through an online questionnaires during November-December 2021.ResultsThe survey was completed by 571 participants from 63 cities. Pulmonologists comprised the majority (35.20%), followed by internal medical specialists (27.85%) and general practitioners (23.29%). The rates of participants who started empirical antibiotics in the outpatient, ward, and ICU (intensive care unit) were 70.2%, 85.5%, and 74.6%, respectively. When the practice of prescribing antibiotics by physicians for the treatment of COVID-19 in outpatients was compared according to the healthcare setting (primary, secondary, tertiary care hospitals) no significant difference was found. Sputum purulence (68.2%) was recognized as the most important factor for the decision of antibiotic therapy, followed by procalcitonin levels (64.9%) and abnormal radiological findings (50.3%). The most prescribed antibiotics were respiratory quinolones. (48%, 65.9%, 62.7% outpatient, ward, ICU respectively)ConclusionsIn this study, we found that physicians frequently had irrational attitudes toward antibiotic prescription to COVID-19 patients, including those with minor diseases. Our findings underline that the necessity of particular, workable interventions to guarantee the prudent use of antibiotics in COVID-19.

Telehealth-Based Information Retrieval and Extraction for Analysis of Clinical Characteristics and Symptom Patterns in Mild COVID-19 Patients

Clinical characteristics of COVID-19 patients have been mostly described in hospitalised patients, yet most are managed in an outpatient setting. The COVID-19 pandemic transformed healthcare delivery models and accelerated the implementation and adoption of telemedicine solutions. We employed a modular remote monitoring system with multi-modal data collection, aggregation, and analytics features to monitor mild COVID-19 patients and report their characteristics and symptoms. At enrolment, the patients were equipped with wearables, which were associated with their accounts, provided the respective in-system consents, and, in parallel, reported the demographics and patient characteristics. The patients monitored their vitals and symptoms daily during a 14-day monitoring period. Vital signs were entered either manually or automatically through wearables. We enrolled 162 patients from February to May 2022. The median age was 51 (42–60) years; 44% were male, 22% had at least one comorbidity, and 73.5% were fully vaccinated. The vitals of the patients were within normal range throughout the monitoring period. Thirteen patients were asymptomatic, while the rest had at least one symptom for a median of 11 (7–16) days. Fatigue was the most common symptom, followed by fever and cough. Loss of taste and smell was the longest-lasting symptom. Age positively correlated with the duration of fatigue, anorexia, and low-grade fever. Comorbidities, the number of administered doses, the days since the last dose, and the days since the positive test did not seem to affect the number of sick days or symptomatology. The i-COVID platform allowed us to provide remote monitoring and reporting of COVID-19 outpatients. We were able to report their clinical characteristics while simultaneously helping reduce the spread of the virus through hospitals by minimising hospital visits. The monitoring platform also offered advanced knowledge extraction and analytic capabilities to detect health condition deterioration and automatically trigger personalised support workflows.

Molnupiravir increases SARS-CoV-2 genome diversity and complexity: A case-control cohort study.

Molnupiravir, an oral direct-acting antiviral effective in vitro against SARS-CoV-2, has been largely employed during the COVID-19 pandemic, since December 2021. After marketing and widespread usage, a progressive increase in SARS-CoV-2 lineages characterized by a higher transition/transversion ratio, a characteristic signature of molnupiravir action, appeared in the Global Initiative on Sharing All Influenza Data(GISAID) and International Nucleotide Sequence Database Collaboration(INSDC) databases. Here, we assessed the drug effects by SARS-CoV-2 whole-genome sequencing on 38 molnupiravir-treated persistently positive COVID-19 outpatients tested before and after treatment. Seventeen tixagevimab/cilgavimab-treated outpatients served as controls. Mutational analyses confirmed that SARS-CoV-2 exhibits an increased transition/transversion ratio seven days after initiation of molnupiravir. Moreover we observed an increased G->A ratio compared to controls, which was not related to apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like (APOBEC) activity. In addition, we demonstrated for the first time an increased diversity and complexity of the viral quasispecies.

Anticoagulation in COVID-19 patients – An updated systematic review and meta-analysis

BackgroundThromboembolic events are common complications of COVID-19. Clinical study results on safety and efficacy of anticoagulation in COVID-19 are controversial. Material and methodsThis report is the second update of our systematic review with meta-analysis on randomized controlled trials (RCTs) comparing standard thromboprophylaxis, intermediate or therapeutic dose anticoagulation or no anticoagulation in COVID-19 in- and outpatients. We searched eligible studies up to 5 October 2023. Certainty of evidence was assessed using GRADE. ResultsFor this update we included fourteen new RCTs and a total of 27 RCTs with 16,789 patients. Certainty of evidence ranged from very low to high depending on outcome and comparison. Standard thromboprophylaxis with low dose anticoagulation may have little or no effect for COVID-19 outpatients compared to no anticoagulation. In inpatients with moderate or severe COVID-19, intermediate dose anticoagulation may decrease any thrombotic events or death, but may increase major bleeding compared to standard thromboprophylaxis. Therapeutic dose anticoagulation decreases thrombotic events or deaths in inpatients with moderate COVID-19, but probably has little or no effect in patients with severe COVID-19 compared to standard thromboprophylaxis with low or intermediate dose anticoagulation. With therapeutic dose anticoagulation, the risk of major bleeding probably increases regardless of COVID-19 severity. We are uncertain on the effect of thromboprophylaxis with low dose anticoagulation compared to no anticoagulation in the post-discharge setting. ConclusionsHospitalized, moderately-ill COVID-19 patients may benefit from intermediate or therapeutic dose anticoagulation, while critically ill patients may not. Risk of major bleeding must be considered.

Molnupiravir for the treatment of COVID-19 outpatients: An updated meta-analysis

BackgroundThe majority of available data on molnupiravir come from an unvaccinated COVID-19 population. Therefore, we conducted this meta-analysis to integrate evidence from recent randomized controlled trials (RCTs) as well as observational studies stratified by vaccination status to determine the clinical efficacy and safety of molnupiravir in COVID-19 outpatients. MethodsWe searched PubMed, Embase, the Cochrane Library, medRxiv, and ClinicalTrials.gov from inception to November 2023. We conducted our meta-analysis using RevMan 5.4 with risk ratio (RR) as the effect measure. ResultsWe included 8 RCTs and 5 observational studies in our meta-analysis. Molnupiravir reduced the risk of all-cause mortality (RR 0.28; 95% CI: 0.20–0.79, I2 = 0%) but did not decrease the hospitalization rate (RR 0.67; 95% CI: 0.45–1.00, I2 = 53%) in the overall population; in the immunized population, no benefits were observed. Molnupiravir lowered the rate of no recovery (RR 0.78; 95% CI: 0.76–0.81, I2 = 0%) and increased virological clearance at day 5 (RR 2.68; 95% CI: 1.94–4.22, I2 = 85%). There was no increase in the incidence of adverse events. ConclusionsMolnupiravir does not decrease mortality and hospitalization rates in immunized patients with COVID-19. However, it does shorten the disease course and increases the recovery rate. The use of molnupiravir will need to be considered on a case-by-case basis in the context of the prevailing social circumstances, the resource setting, drug costs, and the healthcare burden.

Vitamin A Positively Correlates with Secretory Immunoglobulin A: A Cross-Sectional Study in Omicron COVID-19 Outpatients.

Background: Respiratory tract infections remain among the leading causes of mortality worldwide. The COVID-19 pandemic has highlighted the importance of mucosal immunity in defending against infectious agents. Vitamin A is known to influence the production of secretory immunoglobulin A (SIgA) predominantly in the gut, where it is a critical component of the first line of defense on mucosal surfaces. Methods: This cross-sectional study, conducted 14 days post-positive COVID-19 diagnosis, aimed to determine the relationship between the nutritional status of vitamin A and SIgA levels in COVID-19 outpatients. Serum and saliva samples were collected. Vitamin A nutritional status was determined based on the assessment of dietary intake and the analysis of retinol-binding protein 4 (RBP4). SIgA levels were analyzed from salivary samples. In addition, serum antibodies were analyzed. Results: Dietary vitamin A intake and RBP4 levels positively correlated with SIgA. Patients with higher vitamin A intake showed higher SIgA/IgG1 and SIgA/IgG3 ratios, while those with higher RBP4 levels showed higher SIgA/IgM, SIgA/IgG1, and SIgA/IgG2 ratios. Conclusions: These findings underscore a significant correlation between vitamin A nutritional status and SIgA levels in COVID-19 outpatients, which may suggest the potential importance of maintaining optimal vitamin A levels for the prevention of viral infections.

Real-world use of nirmatrelvir-ritonavir in COVID-19 outpatients during BQ.1, BQ.1.1., and XBB.1.5 predominant omicron variants in three U.S. health systems: a retrospective cohort study

Ritonavir-boosted Nirmatrelvir (NMV-r), a protease inhibitor with invitro activity against SARS-CoV-2, can reduce risk of progression to severe COVID-19 among high-risk individuals infected with earlier variants, but less is known about its effectiveness against omicron variants BQ.1/BQ.1.1/XBB.1.5. We sought to evaluate effectiveness of NMV-r in BQ.1/BQ.1.1/XBB.1.5 omicron variants by comparing hospitalisation rates to NMV-r treated patients during a previous omicron phase and to contemporaneous untreated patients. We conducted a retrospective observational cohort study of non-hospitalised adult patients with SARS-CoV-2 infection using real-world data from three health systems in Colorado and Utah, and compared hospitalisation rates in NMV-r-treated patients in a BA.2/BA.2.12.1/BA.4/BA.5 variant-predominant (first) phase (April 3, 2022-November 12, 2022), with a BQ.1/BQ.1.1/XBB.1.5 variant-predominant (second) phase (November 13, 2022-March 7, 2023). In the primary analysis, we used Firth logistic regression with a two-segment (phase) linear time model, and pre-specified non-inferiority bounds for the mean change between segments. In a pre-specified secondary analysis, we inferred NMV-r effectiveness in a cohort of treated and untreated patients infected during the second phase. For both analyses, the primary outcome was 28-day all-cause hospitalisation. Subgroup analyses assessed treatment effect heterogeneity. In the primary analysis, 28-day all-cause hospitalisation rates in NMV-r treated patients in the second phase (n=12,061) were non-inferior compared to the first phase (n=25,075) (198 [1.6%] vs. 345 [1.4%], adjusted odds ratio (aOR): 0.76 [95% CI 0.54-1.06]), with consistent results among secondary endpoints and key subgroups. Secondary cohort analyses revealed additional evidence for NMV-r effectiveness, with reduced 28-day hospitalisation rates among treated patients compared to untreated patients during a BQ.1/BQ.1.1/XBB.1.5 predominant phase (198/12,061 [1.6%] vs. 376/10,031 [3.7%], aOR 0.34 [95% CI 0.30-0.38), findings robust to additional sensitivity analyses. Real-world evidence from major US healthcare systems suggests ongoing NMV-r effectiveness in preventing hospitalisation during a BQ.1/BQ.1.1/XBB.1.5-predominant phase in the U.S, supporting its continued use in similar patient populations. U.S. National Institutes of Health.

Effectiveness and Patient Satisfaction of Telepsychiatry Services for Reducing Anxiety in COVID-19 Outpatients: A Assessor Blinded RCT

Introduction: Given the importance of anxiety management in pandemics, this study evaluated the effectiveness of telepsychiatry in reducing anxiety in outpatients with COVID-19 and their satisfaction. Methods: This RCT was conducted in a health center in which 188 COVID-19 outpatients participated. First, anxiety level was measured in both the intervention (IG) and control (CG) groups using the Beck Anxiety Inventory (BAI). Then, the IG was offered four educational contents via WhatsApp for four consecutive weeks. One month later, participants completed the BAI questionnaire again, and the CG completed a satisfaction questionnaire. Descriptive statistics and Wilcoxon and Chi-square tests were applied. Results: Psychosomatic complications were significantly reduced only in IG, but physical complications were reduced in both groups. Total anxiety also decreased significantly in both groups, but more significantly in IG (p &lt; .001 for IG and p &lt; .039 for CG). The efficacy of telepsychiatry in reducing anxiety in healthcare workers was greater than in other occupational groups. There was no significant relationship between other demographic variables and telepsychiatry effectiveness. Seventy-eight percent of IG participants had a high level of satisfaction and 70.3% expressed a high desire to receive telepsychiatry in the future. The most important advantages of telepsychiatry were observing social distance, saving time, and reducing costs. In addition, The most important challenges were the lack of face-to-face contact, the lack of previous experience, and the late response of the psychologist. Conclusion: Telepsychiatry effectively reduced moderate anxiety related to COVID-19 and provided high satisfaction.