Predicting Deterioration from Wearable Sensor Data in People with Mild COVID-19.

Coronavirus has caused many casualties and is still spreading. Some people experience rapid deterioration that is mild at first. The aim of this study is to develop a deterioration prediction model for mild COVID-19 patients during the isolation period. We collected vital signs from wearable devices and clinical questionnaires. The derivation cohort consisted of people diagnosed with COVID-19 between September and December 2021, and the external validation cohort collected between March and June 2022. To develop the model, a total of 50 participants wore the device for an average of 77 h. To evaluate the model, a total of 181 infected participants wore the device for an average of 65 h. We designed machine learning-based models that predict deterioration in patients with mild COVID-19. The prediction model, 10 min in advance, showed an area under the receiver characteristic curve (AUC) of 0.99, and the prediction model, 8 h in advance, showed an AUC of 0.84. We found that certain variables that are important to model vary depending on the point in time to predict. Efficient deterioration monitoring in many patients is possible by utilizing data collected from wearable sensors and symptom self-reports.

Are patients with Covid-19 at risk of long-term chronic kidney disease?

Background: The relationship between Coronavirus Disease 2019 (COVID-19) and acute kidney injury (AKI) is well-established. However, a comprehensive evaluation of kidney outcomes in the long-term course of COVID-19 is not yet been performed. The aim of this study is to investigate whether chronic kidney disease (CKD) develops within six months after hospital discharge in COVID-19 patients who did not have kidney damage at the time of admission to the hospital. Patients and Methods: This single-center retrospective study investigated a total of 1008 participants selected from 7500 COVID-19 patients with real-time reverse transcription-polymerase chain reaction (RT-PCR) positivity. All patients had mild/moderate or severe COVID-19. Patients were randomly selected from inpatient and outpatient settings. Critical COVID-19 patients were not included. Results: The mean age of the patients was 56.57 ± 16.30 years, and 69.9% of them were male. The comorbidity percentages of the participants were as follows; 19.5% coronary artery disease (CAD), 28.6% diabetes mellitus (DM), 36.2% hypertension (HT), 3.1% cerebrovascular obstruction (CVO), 1.7% malignancy, 2.6% chronic obstructive pulmonary disease (COPD), 9.4% asthma, % 1.7 dementia, 9.9% hyperlipidaemia, and 1.7% hepatitis B virus (HBV). Kidney function tests of these patients at first admission and 6 months later were compared to reveal the relationship between COVID-19 and CKD. Serum glucose, sodium estimated glomerular filtration rate (eGFR), and uric acid levels were found to be high in the post-COVID-19 period (P = 0.001). However, there were a decrease in serum albumin, potassium, alanine aminotransferase (ALT), C-reactive protein (CRP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) levels (P = 0.001). The difference between the first measurement of serum urea and creatinine (Cr) levels and the measurement 6 months later was not statistically significant (P = 0.102 and P = 0.300, respectively). Conclusions: Those who survived the mild/moderate and severe clinical manifestations of COVID-19 did not exhibit any risk of kidney outcomes after the acute phase of the disease, suggesting that the kidney can protect itself over a long period of time.

Comparison of Serum Total IgA Levels in Severe and Mild COVID-19 Patients and Control Group.

BACKGROUND: The present study aimed to compare serum total IgA levels between severe and mild COVID-19 patients' groups and the control group. METHODS: In this cross-sectional study, 216 definite severe COVID-19 patients (as the inpatient group), 183 subjects with positive specific COVID-19 IgG with mild or no symptoms as the (outpatient group), and 203 healthy subjects with negative specific serology, as the control group were investigated. The cases' laboratory data were collected, and thereafter, statistical tests, including independent samples t test, ANOVA test, and post hoc test, were performed using SPSS software version 22. RESULT: The mean ± SD of IgA in all the included subjects was 2.23 ± 0.78 (g/L). According to the obtained results, there were statistically significant changes in IgA among the three study groups (P value < 0.05). This difference was significant between both outpatient and inpatient groups (P value < 0.05). The mean ± SD of serum IgG in all the subjects was calculated as 15.83 ± 5.73 (g/L). A strong statistically significant change was also seen in IgG among all three groups (P value < 0.001). Of note, there was a significant negative correlation between IgG and IgA total titers of the outpatient group (P value = 0.011*r = - 0.188). CONCLUSION: It was shown that the total serum IgA and IgG levels are significantly associated with the severity of COVID-19 infection. As well, we found that total serum IgA and IgG are associated with the severity of illness. Since a low level of IgA is asymptomatic and high frequent in Iran and other countries, we suggest the evaluation of serum IgA levels in high-risk people and strengthening immune system in subjects with a low level of IgA, in order to reduce the rate of death. In this regard, oral or nasal mucosal vaccines in combination with parenteral vaccination are recommended due to increasing immunity versus COVID-19 by further secretion of the IgA antibody and preventing virus transmission.

Timely treatment and higher compliance to traditional Chinese medicine: New influencing factors for reducing severe COVID-19 based on retrospective cohorts in 2020 and 2021.

OBJECTIVE: From the beginning of 2020, our study team formulated a traditional Chinese medicine (TCM) prescription named Sanhanhuashi formula (SHHS) to treat COVID-19 patients. Then we conducted several studies to explore the effectiveness of SHHS formula and other influencing factors on prognosis of disease. The purpose of this study was to describe the trends of patients' characters from 2020 to 2021 based on two separate cohorts, and to explore the influencing factors on incidence of severe COVID-19 conditions, especially the contributions of timely treatment and higher compliance to SHHS formula. METHODS: A retrospective cohort study was conducted in Wuhan, Hubei province and Tonghua, Jilin province. Participants were hospitalized mild to moderate COVID-19 consecutive enrolled patients in Wuhan hospital of traditional Chinese and western medicine (from Feb 13, 2020 to March 8, 2020) and Tonghua central hospital (from Jan 17, 2021 to Feb 5, 2021). Age, sex, time waiting to be hospitalized, medical history, initial symptoms, concomitant medication, and severity of disease were collected. Univariate and multivariate logistic regression were used to explore the associations between various exposures and the outcome, ie. the proportion of patients who were converted to severe status. E-values and its lower control limit (LCL) were calculated for sensitivity analysis. RESULTS: Totally, 176 COVID-19 patients in two hospitals were enrolled. 81 patients were from Wuhan hospital of traditional Chinese and western medicine and 95 from Tonghua central hospital. 42 patients used SHHS formula arrival or exceed 7 days, and 2 (4.8%) progressed to severe condition. Among 134 patients who were exposed SHHS less than 7 days, 18 (13.4%) were converted to severe situation. Compared with those diagnosed in 2020, cases in 2021 were characterized as lower rates of initial symptoms (88.9% vs 35.8%, P < 0.001) and concomitant medications ever widely used, eg. antiviral medicine (71.6% vs 43.2%, P < 0.001), antibiotics (61.7% vs 13.7%, P < 0.001) and Chinese patent medicine (76.5% vs 44.2%, P < 0.001). They also waited less time for hospitalization (median: 12 vs 2 days, P < 0.001). The final multivariate logistic regression model showed that age (> 60 yrs) (OR: 3.943; 95% CI: 1.402-11.086; P = 0.009; E-value = 7.35, LCL:2.15), diagnosis year (OR: 0.165; 95% CI: 0.050-0.551; P = 0.003; E-value=11.6, LCL: 3.03) and SHHS exposure (OR: 0.118; 95% CI: 0.014-0.992; P = 0.049; E-value = 16.43, LCL:1.1) were independent risk factors for predicting severe status. CONCLUSIONS: The profile of COVID-19 patients has changed after one year. In addition to age, diagnosis year and SHHS exposure are two new factors to predict the prognosis of disease. The patients diagnosed in 2021 were mainly benefited from timely treatment. Subsequently, adhere to use SHHS formula a quite longer time reduced the number of severe cases. Therefore, both the current epidemic prevention and control measures and increasing compliance to traditional Chinese medicine are effective ways to reducing severe cases and improving public health.

Altered motor cortex physiology and dysexecutive syndrome in patients with fatigue and cognitive difficulties after mild COVID-19.

BACKGROUND AND PURPOSE: Fatigue and cognitive difficulties are reported as the most frequently persistent symptoms in patients after mild SARS-CoV-2 infection. An extensive neurophysiological and neuropsychological assessment of such patients was performed focusing on motor cortex physiology and executive cognitive functions. METHODS: Sixty-seven patients complaining of fatigue and/or cognitive difficulties after resolution of mild SARS-CoV-2 infection were enrolled together with 22 healthy controls (HCs). Persistent clinical symptoms were investigated by means of a 16-item questionnaire. Fatigue, exertion, cognitive difficulties, mood and 'well-being' were evaluated through self-administered tools. Utilizing transcranial magnetic stimulation of the primary motor cortex (M1) resting motor threshold, motor evoked potential amplitude, cortical silent period duration, short-interval intracortical inhibition, intracortical facilitation, long-interval intracortical inhibition and short-latency afferent inhibition were evaluated. Global cognition and executive functions were assessed with screening tests. Attention was measured with computerized tasks. RESULTS: Post COVID-19 patients reported a mean of 4.9 persistent symptoms, high levels of fatigue, exertion, cognitive difficulties, low levels of well-being and reduced mental well-being. Compared to HCs, patients presented higher resting motor thresholds, lower motor evoked potential amplitudes and longer cortical silent periods, concurring with reduced M1 excitability. Long-interval intracortical inhibition and short-latency afferent inhibition were also impaired, indicating altered GABAB -ergic and cholinergic neurotransmission. Short-interval intracortical inhibition and intracortical facilitation were not affected. Patients also showed poorer global cognition and executive functions compared to HCs and a clear impairment in sustained and executive attention. CONCLUSIONS: Patients with fatigue and cognitive difficulties following mild COVID-19 present altered excitability and neurotransmission within M1 and deficits in executive functions and attention.

Efficacy of single-dose and double-dose ivermectin early treatment in preventing progression to hospitalization in mild COVID-19: A multi-arm, parallel-group randomized, double-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Ivermectin is a known anti-parasitic agent that has been investigated as an antiviral agent against coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy of ivermectin in mild COVID-19 patients. METHODS: In this multi-arm randomized clinical trial conducted between 9 April 2021 and 20 May 2021, a total of 393 patients with reverse transcription-PCR-confirmed COVID-19 infection and mild symptoms were enrolled. Subjects were randomized in a 1:1:1 ratio to receive single-dose ivermectin (12 mg), double-dose ivermectin (24 mg) or placebo. The primary outcome was need for hospitalization. RESULTS: There was no significant difference in the proportion of subjects who required hospitalization between the placebo and single-dose ivermectin groups (absolute difference in the proportions: -2.3 [95% CI = -8.5, 4.1]) and between the placebo and double-dose ivermectin groups (absolute difference in the proportions: -3.9 [95% CI = -9.8, 2.2]). The odds of differences in mean change in severity score between single-dose ivermectin and placebo groups (ORdifference  = 1.005 [95% CI: 0.972, 1.040]; p = 0.762) and double-dose ivermectin and placebo groups (ORdifference  = 1.010 [95% CI: 0.974, 1.046]; p = 0.598) were not statistically significant. None of the six adverse events (including mild dermatitis, tachycardia and hypertension) were serious and required extra action. CONCLUSION: Single-dose and double-dose ivermectin early treatment were not superior to the placebo in preventing progression to hospitalization and improving clinical course in mild COVID-19.

Hanshiyi Formula, a medicine for Sars-CoV2 infection in China, reduced the proportion of mild and moderate COVID-19 patients turning to severe status: A cohort study.

We formulated a traditional Chinese medicine (TCM) prescription, Hanshiyi Formula (HSYF), which was approved and promoted by the Wuhan Municipal Health Commission for treating mild and moderate coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of HSYF on the progression to severe disease in mild and moderate COVID-19 patients. We conducted a retrospective cohort study of patients with mild and moderate COVID-19 in a quarantine station in Wuchang District, Wuhan. Using the real-time Internet information collection application and Centers for Disease Control for the Wuchang District, patient data were collected through patient self-reports and follow-ups. HSYF intervention was defined as the exposure. The primary outcome was the proportion of patients who progressed to a severe disease status, and a stratification analysis was performed. Univariate and multivariate regression analyses were performed to identify influencing factors that may affect the outcome. Further, we used propensity score matching (PSM) to assess the effect of HSYF intervention on the conversion of mild and moderate to a severe disease status. Totally, 721 mild and moderate COVID-19 patients were enrolled, including 430 HSYF users (exposed group) and 291 non-users (control group). No cases in the exposed group and 19 (6.5 %, P < 0.001) cases in the control group progressed to severe disease, and the difference between the two groups (exposed group-control group) was -6.5 % [95 % confidence interval (CI): (-8.87 %, -4.13 %)]. Univariate regression analysis revealed sex (male), age, fever, cough, and fatigue as risk factors for progression to severe disease. After PSM, none of the HSYF users and 7 (4.7 %, P = 0.022) non-users transitioned to severe disease, and the difference between the two groups (exposed group-control group) was -4.7 % [95 % CI: (-8.2 %, -1.2 %)]. Multivariate regression analysis revealed that sex (male) [OR: 3.145; 95 % CI: 1.036-9.545; P = 0.043] and age (> 48 years) [odds ratio (OR): 1.044; 95 % CI: 1.001-1.088; P = 0.044] were independent risk factors for conversion to severe disease. Therefore, HSYF can significantly reduce the progression to severe disease in patients with mild and moderate COVID-19, which may effectively prevent and treat the disease. However, further larger clinical studies are required to verify our results.

Brain effects of mild COVID-19 in healthy young adults: A pilot study.

Rationale and objectives: This study examined the brain effects of mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which are incompletely understood. Our objective was to ascertain within-person changes associated with mild coronavirus disease 2019 (COVID-19) in otherwise healthy adults. Materials and methods: We leveraged existing pre-pandemic baseline neuroimaging and neurocognitive data, and collected follow-up data from uninfected controls and individuals with prior mild COVID-19, during December 2020 and January 2021, when vaccines were not yet available. We compared change during follow-up in patients (n = 5) versus controls (n = 15). Results: We identified a decrease of intracellular volume fraction (ICVF), decrease of isotropic volume fraction (ISO) and decrease of orientation dispersion index (ODI) in multiple inferior frontal regions of interest in COVID-19 patients; this longitudinal change was significantly different from the control group which demonstrated increases in equivalent measures. This pattern suggests injury with neuronal loss and/or inflammation as underlying mechanisms. Neurocognitive studies identified a pattern of cognitive decline (processing speed, executive function, verbal learning, working memory) in patients, that did not reach significance. Conclusion: Our pilot data suggests that mild COVID-19 may result in brain pathology and impact neurocognitive function in younger adults in a manner parallel to prior findings in older individuals. Though findings may not generalize to other SARS-CoV-2 variants, larger longitudinal studies of mild COVID-19 should be undertaken to understand the potential clinical implications of these findings over the longer term.

Myocardial Blood Flow Quantified Using Stress Cardiac Magnetic Resonance After Mild COVID-19 Infection.

BACKGROUND: Severe COVID-19 infection is known to alter myocardial perfusion through its effects on the endothelium and microvasculature. However, the majority of patients with COVID-19 infection experience only mild symptoms, and it is unknown if their myocardial perfusion is altered after infection. OBJECTIVES: The authors aimed to determine if there are abnormalities in myocardial blood flow (MBF), as measured by stress cardiac magnetic resonance (CMR), in individuals after a mild COVID-19 infection. METHODS: We conducted a prospective, comparative study of individuals who had a prior mild COVID-19 infection (n = 30) and matched controls (n = 26) using stress CMR. Stress and rest myocardial blood flow (sMBF, rMBF) were quantified using the dual sequence technique. Myocardial perfusion reserve was calculated as sMBF/rMBF. Unpaired t-tests were used to test differences between the groups. RESULTS: The median time interval between COVID-19 infection and CMR was 5.6 (IQR: 4-8) months. No patients with the COVID-19 infection required hospitalization. Symptoms including chest pain, shortness of breath, syncope, and palpitations were more commonly present in the group with prior COVID-19 infection than in the control group (57% vs 7%, P < 0.001). No significant differences in rMBF (1.08 ± 0.27 mL/g/min vs 0.97 ± 0.29 mL/g/min, P = 0.16), sMBF (3.08 ± 0.79 mL/g/min vs 3.06 ± 0.89 mL/g/min, P = 0.91), or myocardial perfusion reserve (2.95 ± 0.90 vs 3.39 ± 1.25, P = 0.13) were observed between the groups. CONCLUSIONS: This study suggests that there are no significant abnormalities in rest or stress myocardial perfusion, and thus microvascular function, in individuals after mild COVID-19 infection.

Fatigue in healthcare workers with mild COVID-19 survivors in Indonesia.

Persistent symptoms after the coronavirus disease 2019 (COVID-19, known as post-COVID syndrome (PCS), presented an ongoing health burden among COVID-19 survivors, including health workers. The existence of fatigue in mild COVID-19 survivors has not been widely reported. The aim of this study was to present the symptoms of fatigue in healthcare workers who experienced mild COVID-19 and the factors associated with fatigue. A cross-sectional study was conducted at H. Adam Malik General Hospital in Medan, Indonesia, from September to December 2022, included doctors, nurses, ancillary workers, and medical support workers who experienced mild COVID-19. Fatigue was measured by a fatigue assessment scale (FAS). The assessed possible risk factors were gender, age, vaccination history, comorbid, presence of PCS, duration of PCS symptoms, and number of PCS symptoms. The Chi-squared or Fisher's exact tests were used to assess the association between the incidence of fatigue and risk factors. A total of 100 healthcare workers of mild COVID-19 survivors were included. Most of them were nurses (58%), women (81%), and aged 19-30 years old (36%). The majority had incomplete vaccination history (64%), experienced PCS (71%), no comorbidities (61%), and experienced <3 months of PCS symptoms (55%). Mild to moderate fatigue was found in 23% of healthcare workers and only 1% experienced severe fatigue. No significant association was found between gender, vaccination history, and comorbidities with the incidence of fatigue. However, a significant association was observed between age (p=0.021), the presence of PCS (p=0.041), and the number of PCS symptoms (p=0.047) with fatigue incidence. Furthermore, there were significant associations between symptoms of PCS (confusion (p=0.004), insomnia (p=0.001), myalgia (p=0.035), arthralgia (p=0.028), throat pain (p=0.042), headache (p=0.042), and chest pain (p=0.011)) with fatigue. These findings can contribute to providing the necessary support for mild COVID-19 survivors and persistent fatigue.

Comparison of time to negative conversion of SARS-CoV-2 between young and elderly among asymptomatic and mild COVID-19 patients: a cohort study from a national containment center.

Objective: We aimed to study the relationship between age and time to negative conversion of SARS-CoV-2 in patients with asymptomatic and mild forms of COVID-19. Methods: We conducted a cohort study including all patients diagnosed with COVID-19 from the national COVID-19 containment center of Tunisia. Patients were subdivided into two cohorts: (under 60 years) and (over 60 years) and were followed up until PCR negativization. Log rank test and Cox regression were applied to compare time to negative conversion between the old group and the young group. Results: The study included 289 patients with non-severe forms of COVID-19. Age over 60 was significantly associated with delayed negative conversion in male sex (Hazard ratio (HR): 1.9; 95% CI: 1.2-3.07) and among patients with morbid conditions (HR:1.68; 95% CI: 1.02-2.75) especially diabetics (HR: 2.06; 95% CI: 1.01-4.21). This association increased to (HR:2.3; 95% CI: 1.13-4.66) when male sex and comorbidities were concomitantly present and rose to (HR: 2.63; 95% CI: 1.02-6.80) for men with diabetes. Cox regression analysis revealed a significantly delayed negative conversion in symptomatic patients. Significant interaction was observed between gender and age and between age and chronic conditions. Conclusion: Age is associated with delayed negative conversion of viral RNA in certain subgroups. Identifying these subgroups is crucial to know how prioritize preventive strategies in elderly.

The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 (INSL3) in men with mild COVID-19: A longitudinal study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect the male reproductive system as it uses angiotensin-converting enzyme (ACE)2, which is expressed in testicular tissue, as an entry point into the cell. Few studies have evaluated the long-term effects of mild coronavirus disease 2019 (COVID-19) on testicular function, and insulin-like factor 3 (INSL3) levels have not previously been assessed during acute SARS-CoV-2 infection. OBJECTIVES: The aim of the study was to assess the impact of acute SARS-CoV-2 infection on testicular function including INSL3 and the presence of SARS-CoV-2 RNA in semen in non-hospitalised men with mild COVID-19. MATERIALS AND METHODS: This longitudinal study included 36 non-hospitalised SARS-CoV-2-positive men (median age 29 years). Inclusion was within seven days following a positive SARS-CoV-2 reverse-transcription polymerase chain reaction test. Reproductive hormone levels, semen parameters, and the presence of SARS-CoV-2 RNA in oropharyngeal and semen samples were assessed during acute SARS-CoV-2 infection (baseline) and at three- and six-month follow-up. Wilcoxon matched-pair signed-rank (two samples) test was used to assess time-related alterations in reproductive hormone levels and semen parameters. RESULTS: Lower plasma testosterone (T) (total and calculated free (c-fT)) and higher luteinising hormone (LH) concentrations were observed during acute SARS-CoV-2 infection (baseline) compared to three- and six-month follow-up. Consequently, ratios of c-fT/LH were lower at baseline compared to three- and six-month follow-up (p < 0.001 and p = 0.003, respectively). Concomitantly, lower INSL3 concentrations were observed at baseline compared to three-month follow-up (p = 0.01). The total number of motile spermatozoa was also lower at baseline compared to six-month follow-up (p = 0.02). The alterations were detected irrespective of whether the men had experienced SARS-CoV-2-related fever episodes or not. No SARS-CoV-2 RNA was detected in semen at any time point. DISCUSSION AND CONCLUSION: This study showed a reduction in testicular function, which was for the first time confirmed by INSL3, in men mildly affected by SARS-CoV-2 infection. The risk of transmission of SARS-CoV-2 RNA via semen seems to be low. Febrile episodes may impact testicular function, but a direct effect of SARS-CoV-2 cannot be excluded.

Doxycycline vs Hydroxychloroquine + Azithromycin in the Management of COVID-19 Patients: An Open-Label Randomized Clinical Trial in Sub-Saharan Africa (DOXYCOV).

Objective We aimed to compare the safety and efficacy of a doxycycline-based regimen against Cameroon National Standard Guidelines (hydroxychloroquine plus azithromycin) for the treatment of mild symptomatic COVID-19. Methods We conducted an open-label, randomized, non-inferiority trial in Cameroon comparing doxycycline 100 mg, twice daily for seven days versus hydroxychloroquine 400 mg daily for five days and azithromycin 500 mg at day 1 and 250 mg from day 2 through 5 in mild COVID-19 patients. Clinical recovery, biological parameters, and adverse events were assessed. The primary outcome was the proportion of clinical recovery on days 3, 10, and 30. Non-inferiority was determined by the clinical recovery rate between protocols with a 20-percentage points margin. Results One hundred and ninety-four participants underwent randomization and were treated either with doxycycline (n = 97) or hydroxychloroquine-azithromycin (n = 97). On day 3, 74/92 (80.4%) participants on doxycycline versus 77/95 (81.1%) on hydroxychloroquine-azithromycin-based protocols were asymptomatic (p = 0.91). On day 10, 88/92 (95.7%) participants on doxycycline versus 93/95 (97.9%) on hydroxychloroquine-azithromycin were asymptomatic (p = 0.44). On day 30, all participants were asymptomatic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) polymerase chain reaction (PCR) test was negative on day 10 in 60/92 (65.2%) participants who were assigned to doxycycline and in 63/95 (66.3%) participants who were assigned to hydroxychloroquine-azithromycin. None of the participants were admitted for worsening of the disease after treatment initiation. Conclusion Doxycycline 100 mg twice daily for seven days proved to be safe and non-inferior in terms of efficacy when compared to hydroxychloroquine-azithromycin for preventing clinical worsening of mild symptomatic or asymptomatic COVID-19 and achieving virological suppression.

Efficacy of BREATHOX® Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH Study): A Randomized Pilot Clinical Trial.

(1) Background: A high concentration of sodium chloride on in vitro cell culture leads to reduced SARS-CoV-2 replication. Therefore, our aim was to evaluate the effects of inhaling hypertonic NaCl particles (BREATHOX®) on the duration of COVID-19-induced acute symptoms. (2) Methods: A prospective, open label, randomized, standard of care-controlled group (SOC) pilot trial compared inhaled oral and nasal administered BREATHOX® (2.0 mg NaCl, particles size between 1-10 µm), with five or ten inhalations per day for ten days. The primary endpoint was the time to resolve COVID-19-related symptoms. Safety outcomes included adverse clinical and laboratory events. (3) Results: A total of 101 individuals were screened and 98 were randomly assigned to BREATHOX® ten sessions per day (Group 1; 33 patients), BREATHOX® five sessions per day (Group 2; 32 patients), or SOC (33 patients), and followed up for 28 days. There was an association with cough frequency after 10 days BREATHOX® compared to SOC [Group 1: hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.06-3.81; Group 2: HR 2.17, 95% CI 1.17-4.04]. No differences between the groups for the reported symptoms' resolution time were seen after 28 days. After combining both BREATHOX® groups, the period to cough resolution 10 days after randomization was significantly lower than in SOC (HR 2.10, 95% CI 1.20-3.67). An adverse event occurred in 30% of Group 1, 36% of Group 2, and 9% in SOC individuals. One patient from SOC had a serious adverse event. Nasal burning, sore or itchy nose, and dry mouth were considered related to BREATHOX® use and resolved after stopping inhalations. (4) Conclusion: BREATHOX® inhalation is safe and may be effective in reducing the duration of COVID-19-induced coughing.

Favipiravir in the Treatment of Outpatient COVID-19: A Multicenter, Randomized, Triple-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Finding effective outpatient treatments to prevent COVID-19 progression and hospitalization is necessary and is helpful in managing limited hospital resources. Repurposing previously existing treatments is highly desirable. In this study, we evaluate the efficacy of Favipiravir in the prevention of hospitalization in symptomatic COVID-19 patients who were not eligible for hospitalization. METHODS: This study was a triple-blind randomized controlled trial conducted between 5 December 2020 and 31 March 2021 in three outpatient centers in Isfahan, Iran. Patients in the intervention group received Favipiravir 1600 mg daily for five days, and the control group received a placebo. Our primary outcome was the proportion of hospitalized participants from day 0 to day 28. The outcome was assessed on days 3, 7, 14, 21, and 28 through phone calls. RESULTS: Seventy-seven patients were randomly allocated to Favipiravir and placebo groups. There was no significant difference between groups considering baseline characteristics. During the study period, 10.5% of patients in the Favipiravir group and 5.1% of patients in the placebo group were hospitalized, but there was no significant difference between them (p-value = 0.3). No adverse event was reported in the treatment group. CONCLUSIONS: Our study shows that Favipiravir did not reduce the hospitalization rate of mild to moderate COVID-19 patients in outpatient settings.

Household secondary attack rate in mild COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic has reached a staggering number of almost 280 million cases worldwide, with over 5.4 million deaths as of 29 December 2021. A further understanding of the factors related to the household spread of the infection might help to bring about specific protocols to curb such transmission. Objective: This study aims to find the secondary attack rate (SAR) and factors affecting SAR among the households of mild COVID-19 cases. Methods: An observational study was designed where data of patients admitted at All India Institute of Medical Sciences, New Delhi due to mild COVID-19 were collected, and outcome was noted after the discharge of the patient. Index cases who were the first in the household to have a positive infection only were included. Based on these data, the overall household SAR, factors related to the index case and contacts that affected transmissibility were noted. Results: A total of 60 index cases having contacts with 184 household members were included in the present study. The household SAR was measured to be 41.85%. At least one positive case was present in 51.67% households. Children below 18 years old had lower odds of getting a secondary infection compared to adults and elderly [odds ratio (OR) = 0.46, 95%CI = 0.22-0.94, p = 0.0383). An exposure period of more than a week was significantly associated with a higher risk of infection (p = 0.029). The rate of transmissibility drastically declined with effective quarantine measures adopted by the index case (OR = 0.13, 95%CI = 0.06-0.26, p < 0.00001). Symptomatic index cases contributed more to the SAR than asymptomatic primaries (OR = 4.74, 95%CI = 1.03-21.82, P = 0.045). Healthcare worker index cases had lower rates of spread (OR = 0.29, 95%CI = 0.15-0.58, P = 0.0003). Conclusion: The high SAR shows the household is a potential high-risk unit for transmissibility of COVID-19. Proper quarantine measures of all those exposed to the index case can mitigate such spread and lead to reduction of risk of COVID-19 within a household.

Gestational Mild COVID-19 Infection Associated Neonatal Hearing Loss: A Case-Control Study from North India.

COVID-19 infection during pregnancy is potentially dangerous to neonatal hearing, as it is the period of organogenesis, and associated hyperthermia may cause vascular damage, disruption of cell migration, and death of the dividing neuroblasts. To investigate the possible association between neonatal hearing loss and gestational mild COVID-19 infection. A prospective case-control study was conducted at a tertiary healthcare centre in North India from March 2020 to Oct 2022. Cases included the neonates born to COVID-19-positive mothers were subjected to hearing screening at 1, 3 and 6 months using otoacoustic emission (OAE) and automated auditory brainstem response (AABR). Similar protocol was applied to controls, i.e., neonates borne to mothers with no gestational history of COVID infection. Results were analyzed statistically. Our study reported that the statistical difference between groups A (n = 942) and B (n = 942) for gestational COVID-19 infection and neonatal hearing loss was insignificant at 1 month (p-value 0.272 for OAE and p-value 0.634 for AABR) and also insignificant at 3 and 6 months (p-value 0.679 for AABR, for both). The association between gestational mild COVID-19 infection during gestation and neonatal hearing loss is statistically insignificant at initial screening as well as sequential screenings.

Catastrophic Concomitant Arterial and Venous Thrombosis in a Mild COVID-19-Positive Patient.

Since its first discovery in late 2019, coronavirus disease 2019 (COVID-19) has been a global burden associated with significant morbidity and mortality. COVID-19 has been correlated with the development of hypercoagulable state that predisposes the patients to a higher risk of thromboembolism. Current evidence suggests higher incidence of thrombosis, particularly venous thrombosis, among hospitalized COVID-19 patients, mostly with critical illness. On the other hand, there is currently no data regarding the incidence of vivid thrombosis in ambulatory patients with mild COVID-19 and the incidence of concomitant arterial and venous thrombosis in COVID-19 is extremely rare. Herein, we describe catastrophic outcomes of concomitant lower limb arterial and venous thrombosis in a patient with mild COVID-19. This report highlights the occurrence of concomitant arterial and venous thrombosis in ambulatory setting and that this phenomenon resulted in catastrophic clinical consequences.

Balance Ability and Quality of Life in Older Adult with Recovery from Mild COVID-19.

BACKGROUND: In this study, we aimed to assess the ability to balance and quality of life (QoL) among older adults without a history of coronavirus disease 2019 (COVID-19) and those who had recovered from mild COVID-19. METHODS: We recruited 80 older adults and categorized them into the following two groups based on their history of COVID-19: those without COVID-19 (n=40) and those who had recovered from mild COVID-19 (n=40). We assessed the participants' ability to balance using the multi-directional reach test and timed up and go (TUG) test, and evaluated their QoL using the Short Form-36. RESULTS: Compared with older adults without a history of COVID-19, those who had recovered from mild COVID-19 demonstrated no differences in the scores of the forward, backward, right, and left directions (p>0.05), but a significantly longer duration for the TUG test (p=0.02) and a reduced QoL. CONCLUSION: Our study results demonstrated decreased ability to balance and poor QoL among older adults who had recovered from mild COVID-19.