Severe COVID-19 Pneumonia Research Articles

The effect of corticosteroids in developing active pulmonary tuberculosis among patients with COVID-19.

Corticosteroids can reduce the mortality rate among patients with severe COVID-19 pneumonia. However, opportunistic infections such as Mycobacterium tuberculosis are of concern, especially among those on high doses of corticosteroids. It is unknown whether the risk of developing subsequent TB infection is high or not among COVID-19 patients on high doses of corticosteroids. Hence, this study was conducted to address this gap of knowledge. We conducted a retrospective, cross-sectional study at the King Chulalongkorn Memorial Hospital from October 12, 2022 to June 30, 2023. Two hundred forty-three participants with documented COVID-19 diagnosis on high dose corticosteroids were enrolled into the study. Baseline characteristics and risk factors of developing TB were collected. The prevalence of TB was significantly different among participants with chronic kidney disease (CKD) stages 2-4 and chronic lung diseases. The incidence of TB post 1-year diagnosis of COVID-19 was 4 out of 243 patients (1.6%) or 1,646 cases per 100,000 person-year. The mortality rate among subsequent TB group was significantly much higher than the non-TB group (50% vs 0.4%; p-value = 0.001). COVID-19 participants on high doses of corticosteroids also were co-infected with other infections such as bacteria (37.1%), fungi (5.3%), and Pneumocystis jirovecii (PJP) (1.2%). We found that the incidence of TB in participants with COVID-19 on high doses of corticosteroids was 11 times higher than the general population. Therefore, we recommend screening for latent TB among these patients to prevent/early diagnose TB disease.

Pulmonary fibrosis followed by severe pneumonia in patients with COVID-19 infection requiring mechanical ventilation: a prospective multicentre study

BackgroundsThe management of lung complications, especially fibrosis, after COVID-19 pneumonia, is an important issue in the COVID-19 post-pandemic era. We aimed to investigate risk factors for pulmonary fibrosis development in...

Predictors of Chest CT Total Severity Score InCovid-19 Infected Patients In Rwanda

Background: Over 5.54 million COVID-19 deaths occurred worldwide by the January 2021 and COVID-19 pneumonia remains the commonest cause of death. The current study was conducted to investigate predictors of total severity score in patients with COVID-19 pneumonia who underwent chest CT and in turn be used in setting with limited resource to predict TSS as well as prognosis Materials and Methods: The current study retrospectively evaluated the CT findings in COVID-19 patients with clinical severity using a 25-point visual quantitative assessment and total severity score predictors were determined. A sample of 384 COVID-19 patients was used and Statistical analysis was done using SPSS 25.0. Results: The findings of the current study indicate that age (p < 0.001), vaccination status (p = 0.006), and disease status (p < 0.001) are significant predictors of the total severity score on chest CT scans in patients with COVID-19 pneumonia. Specifically, as age increases, the odds of having a higher total severity score also increase. Conversely, individuals who are vaccinated tend to have lower severity scores, suggesting that COVID-19 vaccination is associated with a reduced likelihood of experiencing severe disease. Additionally, patients with severe COVID-19 pneumonia are more likely to exhibit higher severity scores on Chest CT. Conclusion: Chest CT scan total severity score can be predicted with age, immunization status and disease status classified as mild, moderate, severe and critical covid-19 pneumonia and this score can be used to predict clinical outcome. Recommendation: A large multicenter study can be used to validate current study findings and these clinical predictors can be used in resource limited settings where CT scan accessibility is not ensured.

Neuropsychiatric symptoms of patients two years after experiencing severe COVID-19: A mixed observational study

BackgroundThe impact of SARS-CoV-2 infection (COVID-19) on mental health has not been extensively studied in the medium and long term. This study assessed how clinical, biological, and social factors affect mental health in patients who recovered from severe COVID-19. The evaluation was done 90 days after hospital discharge and followed up at 12 and 24 months. MethodsA retrospective-prospective cohort mixed observational study was conducted on patients over 18 years of age who required hospitalization in Internal Medicine or ICU for severe COVID-19 pneumonia during 2020 and 2021. Demographic information, clinical variables, and data for the scales were obtained from electronic medical records and telephone interviews. For comparisons of the different variables in each clinical variable (insomnia, depression, anxiety), the Student's t-test for independent samples has been used (normal distribution); otherwise, the Mann–Whitney test will be used. All tests and intervals will be performed with a confidence level of 95. Fisher's exact or Pearson's Chi-square test has been used as appropriate for qualitative variables. Results201 patients were recruited. 37.3% presented insomnia, 22.4% anxiety, and 21.4% depressive symptoms. A direct association was established between female sex and depressive symptoms. Psychotropic history, fatigue, and C-reactive protein levels (CRP) were correlated with depression. Anosmia and ageusia, CRP, cognitive symptoms, and dyspnea predicted insomnia. Sex, orotracheal intubation (OTI), pain, fatigue, mental health history, and academic level were independent predictors of anxiety. High percentages of depressive, anxiety, and insomnia symptoms were detected in the second month after discharge and persisted at 12 and 24 months. The fatigue variable maintained a significant relationship with depressive symptoms at 2, 12 and 24 months. A possible limitation could be recall bias in retrospective data collection. ConclusionsThis is a novel study to follow up on mental health for two years in patients with severe COVID-19. Clinical, biological, and psychosocial variables could be predictors of depressive symptoms, anxiety, and insomnia. The psychiatric symptoms persisted throughout the 2-year follow-up. These findings are critical for the follow-up of these patients and open the possibility of further studies in the medium and long term.

Challenges in Diagnosis of COVID-19 Pneumonia under Ocrelizumab and De-Risking Strategies in Multiple Sclerosis—The Elephant Is (Still) in the Room

Severe SARS-CoV-2 infections may still be observed in people bearing risk factors, such as the use of anti-CD20 monoclonal antibodies (mAbs), which are adopted in several autoimmune disorders including multiple sclerosis (MS). COVID-19 diagnosis is routinely based on nasopharyngeal swab testing, but suboptimal sensitivity for SARS-CoV-2 detection compared to bronchoalveolar lavage (BAL) may lead to misdiagnosis in some cases. Such diagnostic issues were described in a few MS patients receiving anti-CD20 mAbs, including middle-aged people and lacking information on subsequent MS therapeutic management, a debated topic as no evidence-based guidance on de-risking strategies is currently available. Here, we report the case of a young MS patient who developed severe COVID-19 pneumonia under treatment with the anti-CD20 mAb ocrelizumab, and who was finally diagnosed with SARS-CoV-2 by BAL despite repeatedly negative nasopharyngeal swabs. Ocrelizumab was then discontinued, and treatment with a sphingosine-1 phosphate receptor modulator was started, followed by maintenance of clinical and radiological MS stability. Challenges in diagnosing COVID-19 pneumonia in people without risk factors other than immunomodulatory treatment are hence discussed, as well as potential strategies for de-risking MS therapies. The latter topic is increasingly debated based on raising concerns for potential long-term safety issues of high-efficacy treatments, including anti-CD20 mAbs.

Cyclosporin A as an Add-On Therapy to a Corticosteroid-Based Background Treatment in Patients with COVID-19: A Multicenter, Randomized Clinical Trial.

Background: In susceptible hosts, SARS-CoV2-induced hyperinflammation accounts for an increased mortality. The search of adjuvant immunomodulatory therapies has been ongoing ever since the pandemic outbreak. Aim: Our purpose was to evaluate the efficacy of cyclosporin A (CsA) as an add-on therapy to the standard of care (SoC) in patients with severe COVID-19 pneumonia. Methods: We conducted a randomized clinical trial in patients admitted to eight Spanish tertiary hospitals. Patients were stratified into two severity categories and randomized in a 1:1 ratio to receive a corticosteroid-based standard therapy with or without CsA. The primary endpoint was FiO2 recovery by Day 12 without relapses. Results: 109 patients were included and randomized, and 98 of them considered for the mITT population (51 assigned to the CsA + SoC group and 47 to the SoC group). A total of 35 (68.6%) patients from the CsA + SoC group and 32 (71.1%) patients from the SoC group reached the primary endpoint in the mITT analysis. No differences were found after stratification into age groups, in the severity level at admission, or in a combination of both. Overall, the time to FiO2 normalization was 7.4 days vs. 7.9 days in the experimental and control groups, respectively. Global mortality was 8.2%. Severe adverse events were uncommon and equally distributed between arms. Conclusion: The addition of CsA did not show differences over a corticosteroid-based treatment in the clinical course of the included patients. A better identification of candidates who will benefit from receiving immunomodulatory drugs is necessary in future studies.

Tocilizumab in combination with standard of care in patients with severe COVID-19 pneumonia: Efficacy and safety from a phase 3 clinical trial in Japan

BackgroundCoronavirus disease 2019 (COVID-19) is characterized by high interleukin-6 levels. Clinical data supporting tocilizumab, a monoclonal antibody that targets interleukin-6 receptor-alpha, for treating Japanese patients with severe COVID-19 pneumonia are needed. MethodsThis single-arm phase 3 study investigated tocilizumab (8 mg/kg) plus standard of care (SOC) in Japanese patients hospitalized with severe COVID-19 pneumonia. Clinical status was assessed using a 7-category ordinal scale on day 28 (primary endpoint) and day 14 (secondary endpoint). Other secondary endpoints were time to improvement (≥2 category improvement) and time to hospital discharge. Safety was assessed as the incidence of adverse events (AEs). ResultsAmong 48 patients enrolled, 44 (91.7 %) scored ≥3 on the 7-category ordinal scale at baseline. At day 28, 35 patients (72.9 %) scored 1 and 5 (10.4 %) scored 7 on the 7-category ordinal scale; 36 (75.0 %, 95 % confidence interval [CI]: 60.40 %–86.36 %) and 39 (81.3 %, 95 % CI: 67.37 %–91.05 %) patients achieved ≥2- and ≥1-category improvement, respectively; 6 patients (12.5 %, 95 % CI: 4.73 %–25.25 %) demonstrated ≥1-category worsening. At day 14, 25 (52.1 %, 95 % CI: 37.19 %–66.71 %) and 33 patients (68.8 %, 95 % CI: 53.75 %–81.34 %) achieved ≥2- and ≥1-category improvement, respectively; 5 patients (10.4 %, 95 % CI: 3.47 %–22.66 %) demonstrated ≥1-category worsening. Median times (95 % CI) to improvement and hospital discharge were 11 (9–15) and 15 (11–18) days, respectively. Forty patients (83.3 %) experienced AEs; the incidence of ≥grade 3 AEs was 25 %. ConclusionTocilizumab plus SOC may provide improved clinical status in Japanese patients with severe COVID-19 pneumonia; no new safety signals were identified.

90-Day outcomes in patients with severe COVID-19 pneumonia treated with invasive mechanical ventilation

BackgroundThere are few reports detailing the prognostic factors of severe COVID-19 pneumonia requiring invasive ventilation. We investigated the long-term prognosis and evaluated which factors influenced outcomes in these patients. MethodsData was reviewed from severe adult COVID-19 cases admitted to our hospital and treated with mechanical ventilation between February 1, 2020, and October 30, 2021. On admission to our hospital, comorbidities and laboratory findings were collected from clinical records. Prognostic information for 90 days after diagnosis was also obtained from hospitals where patients were transferred after their conditions stabilized. ResultsPrognostic information was obtained in 133 patients, of which 106 were males (79.7 %). Of the 133 patients, 67 were discharged (51.5 %), 21 continued inpatient care (15.8 %), and 45 died (33.8 %). Age, Charlson Risk Index, and the number of patients on hemodialysis were significantly higher in the deceased group. There were no differences in therapeutic interventions between survivors and those who died except for a higher rate of muscle relaxant and vasopressor usage in the deceased group. Laboratory findings on admission showed significantly higher levels of BUN, creatinine, and serum Krebs von den Lungen 6 (KL-6), and significantly lower platelet counts, hemoglobin, and alanine aminotransferase in those who died. Multivariate analysis revealed that age, hemodialysis, lower platelet counts, and higher KL-6 were independent predictors for 90-day mortality. ConclusionsOlder age, hemodialysis, lower platelet counts and high KL-6 on admission were identified as independent predictors of 90-day mortality in patients with respiratory failure due to severe COVID-19 under invasive mechanical ventilation.

A tailored machine learning approach for mortality prediction in severe COVID-19 treated with glucocorticoids.

<sec><title>BACKGROUND</title>The impact of severe COVID-19 pneumonia on healthcare systems highlighted the need for accurate predictions to improve patient outcomes. Despite the established efficacy of glucocorticoids (GCs), variable patient responses are observed, and the existing clinical scores are limited in predicting non-responders. We propose a machine learning (ML) based approach to predict mortality in COVID-19 pneumonia treated with GCs.</sec><sec><title>METHODS</title>This is an ML-driven retrospective analysis involving 825 patients. We leveraged XGBoost to select the most appropriate features from the initial 52, including clinical and laboratory data. Six different ML techniques were compared. Shapley additive explanation (SHAP) values were used to describe the influence of each feature on classification. Internal validation was performed.</sec><sec><title>RESULTS</title>Nine key predictors of death were identified: increasing C-reactive protein (CRP), decreasing arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO₂/FiO₂), age, coronary artery disease, invasive mechanical ventilation, acute renal failure, chronic heart failure, PaO₂/FiO₂ earliest value, and body mass index. Random forest achieved the highest test area under the receiver operating characteristic curve at 0.938 (95% CI 0.903-0.969). SHAP values highlighted age and PaO₂/FiO₂ improvement as the most influential features; the latter showed a higher impact than CRP reduction over time.</sec><sec><title>CONCLUSION</title>The proposed ML algorithm effectively predicts the risk of hospital death in COVID-19 pneumonia patients undergoing GCs. This approach can be adapted to datasets measuring similar clinical variables.</sec>.

COVID-19 and pregnancy: impact, outcomes, and potential therapy

The impact of the new coronavirus COVID-19 infection on the course of pregnancy, maternal and child health is largely unclear and controversial. The presented literature review analyzes changes in the immune, cardiovascular, and endocrine systems in women in physiological pregnancy. The peculiarities of the course of infection caused by SARS-CoV-2 virus in pregnancy, depending on the virus variant, are presented, the issues of infection pathways into immune and non-immune cells, including placental cells, as well as the issues of transplacental transfer of the virus – the key moment of infection of the embryo or fetus, on which the outcome of pregnancy also largely depends, are considered. Promising approaches to COVID-19 therapy are presented: use of inhibitors of transmembrane serine protease 2 (TMPRSS2), furin, angiotensin-converting enzyme (ACE2) and RNA-dependent RNA polymerase, amnion epithelial cells and their exosomes. At the same time, the potential use of mesenchymal stem cells in patients with severe COVID-19 pneumonia is reviewed. Difficulties and questions regarding the use of the above therapeutic methods in pregnant women are highlighted. Aspects of the use of surfactant preparations in newborns at risk of new coronavirus infection are considered.

Predictors of the presence of radiological abnormalities 6 months after severe COVID-19 pneumonia

BackgroundSARS-CoV-2 pneumonia can cause significant long-term radiological changes, even resembling pulmonary fibrosis. However, the risk factors for these long-term effects are unknown. This study aims to assess radiological abnormalities and their possible risk factors six months after hospital discharge due to COVID-19 pneumonia.Material and methodsThis cross-sectional study in a tertiary hospital included adults admitted for COVID-19 pneumonia from March 2020 to February 2021, who underwent high-resolution computed tomography (HRCT) scans of the chest six months after hospital discharge. The primary outcome was radiological abnormalities on HRCT, while the main explanatory variables were drawn from the patient’s medical history along with the disease course, analytical indicators, and the treatment received during admission.ResultsThe 189 included patients had a mean age of 61.5 years; 70.9% were male, and hypertension was the main comorbidity (45%). About two-thirds (67.2%) presented acute respiratory distress syndrome (ARDS). Most (97.9%) received systemic corticosteroid therapy, and 81% presented pathological findings on HRCT, most commonly ground glass (63.5%), followed by bronchial dilatation (36%) and subpleural bands (25.4%). The multivariable analysis showed that age was the main risk factor, associated with most radiological changes. Other factors were the duration of corticosteroid therapy for ground glass (adjusted odds ratio [aOR] 1.020) as well as a longer stay in the intensive care unit (ICU) (aOR 1.290) and high levels of IL-6 for bronchial dilation (aOR 1.002). ConclusionRadiological involvement of the lungs six months after COVID-19 pneumonia is frequent, especially ground glass. Elderly patients with prolonged ICU admission and a significant inflammatory response measured by IL-6 are more likely to present worse radiological evolution and are candidates for radiological follow-up after COVID-19 pneumonia.

Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements.

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Clinical and Genomic Perspective of SARS CoV-2 Infection in Liver Disease Patients: A Single-Centre Retrospective Study.

The limited literature on the clinical course of COVID-19 among patients with underlying liver disease (LD) is available from India. The present study aimed to evaluate the clinical and mutational profile of SARS-CoV-2 among LD cases. This was a retrospective study including admitted LD cases in whom SARS-CoV-2 RT-PCR testing was performed. Complete demographic and clinical details were retrieved from Hospital Information System. Detailed mutational analysis was performed by comparing LD COVID-19 positive study group, i.e. LD-CoV(+) with COVID-19 positive outpatients without any underlying LD as control, i.e. NLD-CoV(+). Out of 232 enrolled LD cases, 137 (59.1%) were LD-CoV(+). LD cases with existing co-morbidities were affected more (P = 0.002) and had 2.29 times (OR 2.29, CI 95%, 1.25-4.29) higher odds of succumbing to COVID-19 (P = 0.006). On multivariate regression analysis, ascites (P = 0.05), severe COVID-19 pneumonia (P = 0.046), and an increased levels of bilirubin (P = 0.005) and alkaline phosphatase (P = 0.003) were found to be associated with adverse outcome in LD-CoV(+).On mutational analysis, we found certain differences between LD- and NLD-CoV(+) infected with Delta [LD- and NLD-CoV (+ /D)] and Omicron [LD- and NLD-CoV(+/O)]. More mutations were shared between LD- and NLD-CoV(+/O) compared to LD- and NLD-CoV(+/D). There were differences in prevalence of indel mutations specific to LD-CoV ( +) for both Delta and Omicron. Moreover, we also reported an interesting genic bias between LD- and NLD-CoV( +) in harbouring deleterious/tolerated mutations. To conclude, LD cases with comorbidities were affected more and had higher odds of mortality due to COVID-19. The definite difference between LD- and NLD-CoV(+) groups with respect to frequency of harboured mutations and an inherent genic bias between them is of noteworthy importance.

Acute kidney injury and COVID-19: the predictive power of BUN/albumin ratio for renal replacement therapy requirement.

To investigate the predictive power of the BUN/albumin ratio (BAR) measured in the emergency department (ED) for the requirement of renal replacement therapy (RRT) in patients admitted to the intensive care unit (ICU) with severe COVID-19 pneumonia and acute kidney injury (AKI). The study included 117 patients with AKI who were admitted to the ICU and had COVID-19 pneumonia detected on chest computed tomography (CT) taken in the ED's pandemic area between November 1, 2020, and June 1, 2021. The predictive power of laboratory values measured at the time of ED admission for the requirement of RRT was analyzed. Of the patients, 59.8% (n = 70) were male, with an average age of 71.7 ± 14.8years. The mortality rate of the study was 35% (n = 41). During follow-up, 23.9% (n = 28) of the patients required RRT. Laboratory parameters measured at the time of ED admission showed that patients who required RRT had significantly higher BAR, BUN, and creatinine levels, and significantly lower albumin levels (all p < 0.001). ROC analysis to determine the predictive characteristics for RRT requirement revealed that the BAR had the highest AUC value (AUC, 0.885; 95% CI 0.825-0.945; p < 0.001). According to the study data, for BAR, a cut-off value of 1.7 resulted in a sensitivity of 96.4% and a specificity of 71.9%. In patients with severe pneumonia who develop acute kidney injury, the BUN/albumin ratio may guide clinicians early in predicting the need for renal replacement therapy.

Insight Into Severe Neonatal COVID-19 Gained Through Whole Exome Sequencing of Twin Neonates.

The genetic basis of neonatal COVID-19 infection, which exhibits a range of severity, has not been investigated. We identified both shared and unique genetic variants involved in antiviral immune responses through whole exome sequencing of an infant who developed severe COVID-19 pneumonia and multisystem inflammatory syndrome and the twin brother also positive for severe acute respiratory syndrome-coronavirus-2, but with only moderate respiratory symptoms.

Respiratory Worsening at the End of a Hospital Stay for Severe Covid19 Pneumonia Revealing Pulmonary Tuberculosis

The coexistence of a viral and tuberculous respiratory infection increases mortality and the transition to a severe form in both directions. We report an observation for a 55-year-old woman with untreated diffuse interstitial pnuemopathy, investigated by immunological and infectious tests, and found negative for pulmonary tuberculosis. Bronchial biopsies revealed non-specific inflammation, responsible for chronic dyspnea. Having presented ten days previously with myalgias, fatigue, dry cough and fever, with worsening of basic dyspnoea, without digestive or neurological manifestations, she was referred to the emergency department, where physical examination showed SpO2 at 80% on room air, reduced to 92% under 15 L/mn delivered via a high-concentration mask, polypnoea at 40 cycles per minute with bilateral diffuse crackling rales on auscultation, scattering just the anterior quadrants. The initial evolution was favorable, with clinical improvement in oxygen saturation to 94% on two liters per minute of oxygen delivered by nasal cannula, with respiratory rate at 23 cycles per minute with modest effort tolerance. On day 18 of hospitalization, she presented with a febrile peak of 38.3°C, polypnoea at 33 cycles per minute, increased oxygen requirements with a flow rate of 6l/m by face mask to reach an oxygen saturation of 92%, tachycardia at 130 beats per minute, and was therefore readmitted to intensive care with high-flow nasal oxygen therapy and antibiotic therapy with imipenem and amikacin. Multiplex PCR showing no germ, and a PCR test for pulmonary tuberculosis on a sputum sample which was positive, prompting the introduction of antibacillary treatment based on a fixed quadric-association of rifampicin, isoniaside, pyrazinaamide and ethombutol. Non-specific antibiotic therapy was discontinued after improvement of the inflammatory syndrome, and antibacillary treatment is still ongoing. Conclusion: Through this observation we discuss the difficulties in terms of diagnosis, management and outcome of a coinfection by SARS-COV 19 and mycobacterium tuberculosis.

SARS-CoV-2 viremia but not respiratory viral load is associated with respiratory complications in patients with severe COVID-19

BackgroundSevere COVID-19 carries a high morbidity and mortality. Previous studies have shown an association between COVID-19 severity and SARS-CoV-2 viral load (VL). We sought to measure VL in multiple compartments (urine, plasma, lower respiratory tract) in patients admitted to the intensive care unit (ICU) with severe COVID-19 pneumonia and correlate with clinical outcomes.MethodsPlasma, urine, and endotracheal aspirate (ETA) samples were obtained on days 1, 3, 7, 14, and 21 from subjects admitted to the ICU with severe COVID-19. VL was measured via reverse transcriptase polymerase chain reaction. Clinical data was collected from the electronic health record. Grouped comparisons were performed using Student’s t-test or 1-way ANOVA. Linear regression was used to correlate VL from different compartments collected at the same time. Logistic regression was performed to model ventilator-freedom at 28 days as a function of peak plasma VL.ResultsWe enrolled 57 subjects with severe COVID-19 and measured VL in plasma (n = 57), urine (n = 25), and ETA (n = 34). Ventilator-associated pneumonia developed in 63% of subjects. 49% of subjects were viremic on study day 1. VL in plasma and ETA both significantly decreased by day 14 (P < 0.05), and the two were weakly correlated on study day 1 (P = 0.0037, r2 = 0.2343) and on all study days (P < 0.001, r2 = 0.2211). VL were not detected in urine. While no associations were observed with peak ETA VL, subjects with higher peak plasma VL experienced a greater number of respiratory complications, including ventilator-associated pneumonia and fewer ventilator-free and hospital-free days. There was no association between VL in either plasma or ETA and mortality. In viremic patients, plasma VL was significantly lower in subjects that were ICU-free and ventilator-free (P < 0.05), with trends noted for hospital-freedom, ventilator-associated pneumonia, and survival to discharge (P < 0.1). By logistic regression, plasma VL was inversely associated with ventilator-freedom at 28 days (odds ratio 0.14, 95% confidence interval 0.02–0.50).ConclusionsElevated SARS-CoV-2 VL in the plasma but not in the lower respiratory tract is a novel biomarker in severe COVID-19 for respiratory complications.

Patterns of thyroid gland dysfunction among hospitalized patients with COVID-19 pneumonia

BackgroundSince the onset of the COVID-19 pandemic, multiple studies have reported a bidirectional between COVID-19 and dysfunction of the thyroid gland. These studies have identified various forms of thyroid dysfunction that have been found to affect the severity and outcome of COVID-19 infection. However, the data from these studies have been inconsistent and conflicting. Our objective was to assess the prevalence of various types of thyroid dysfunction among moderate to severe cases of COVID-19 pneumonia. In addition, the study aimed to evaluate the outcome of thyroid dysfunction after recovery from COVID-19 infection.Patient and methodsIn this observational prospective study data on the clinical features of individuals with moderate to severe COVID-19 pneumonia who were admitted to Zagazig University isolation hospitals from April to December 2022 and their laboratory results were gathered and examined. Thyroid function tests, including TSH, FT3, and FT4, were conducted for all patients upon admission. Follow-up testing was performed on patients who initially had aberrant thyroid lab results 90 days after recovering from COVID-19 infection.ResultsThe study comprised a total of 136 patients who had moderate (44.1%) to severe (55.9%) COVID-19 infection. Sick euthyroid syndrome was the most prevalent form of thyroid dysfunction, accounting for 58.7% of patients with thyroid disorders on admission. After 90 days of post-COVID-19 examination, thyroid dysfunction recovery was observed in 61% of cases. A statistically significant correlation was noted between the severity of COVID-19 and the levels of TSH, free T3, and the ratio of free T3 to T4. A large percentage of patients who showed complete recovery had sick euthyroid syndrome. All patients diagnosed with primary hypothyroidism maintained their hypothyroidism condition, whereas those with hyperthyroidism showed complete recovery.ConclusionCOVID-19 patients may experience several patterns of thyroid dysfunction, including nonthyroidal illness syndrome. These dysfunctions are associated with the intensity of the inflammatory response and the severity of the COVID-19 infection. Nevertheless, these alterations are predominantly reversible upon recovery from a COVID-19 infection.

Heart rate variability and mortality in critically ill COVID-19 pneumonia patients

BackgroundHeart rate variability (HRV) has prognostic value for predicting mortality in both cardiovascular and sepsis patients. Decreased HRV has been associated with increased mortality and morbidity. However, the prognostic significance of HRV in critically ill patients COVID-19 pneumonia still remains unknown. The current study aimed to (1) evaluate prognostic utility of HRV parameters on outcomes in patients with severe COVID-19 pneumonia and (2) assess the correlation between HRV parameters and inflammatory markers. MethodsConsecutive critically ill patients with COVID-19 pneumonia admitted to a tertiary referral intensive care unit from October 2021 to June 2022 in Bangkok, Thailand were enrolled. HRV parameters over the 24 h following intensive care unit admission were recorded using telemetry and analyzed using the Holter program (Philips Holter 2010 Plus/1810 Series). Receiver-operating characteristic (ROC) curve analysis was used to determine optimum threshold cutoffs of various HRV parameters. Formal comparisons of in-hospital mortality between patients with and without a decrease in HRV were performed using Cox regression after adjusting for potential confounders. ResultsA total of 65 patients were enrolled in the study. Patients were classified into two groups: survivors (n = 44, 68 %) and non-survivors (n = 21, 32 %). The standard deviation of normal-to-normal intervals (SDNN) was significantly lower in non-survivors than in survivors (70.30 vs. 105.95; p = 0.03). The SDNN predicted in-hospital mortality with an area under the ROC curve of 0.67 (95 % CI 0.55–0.79). At a cutoff of 70 ms, the SDNN showed a sensitivity and specificity of 0.48 and 0.86. The low SDNN group (<70 ms) demonstrated higher median ferritin, IL-6, and hs-C-reactive protein levels than did the normal SDNN group, although such differences did not reach statistical significance (1139.0 vs. 508.4; p = 0.137 and 91.2 vs. 64.4; p = 0.352, respectively). After adjusting for potential confounders in the multivariable model, the adjusted hazard ratio for in-hospital mortality in those with SDNN <70 ms was 3.70 (95 % CI 1.34–10.24). ConclusionA decrease in SDNN, a commonly used HRV parameter, was associated with mortality and inflammatory biomarkers in critically ill patients with COVID-19 pneumonia.

Anti-inflammatory therapy with nebulized dornase alfa for severe COVID-19 pneumonia: a randomized unblinded trial.

Prinflammatory extracellular chromatin from neutrophil extracellular traps (NETs) and other cellular sources is found in COVID-19 patients and may promote pathology. We determined whether pulmonary administration of the endonuclease dornase alfa reduced systemic inflammation by clearing extracellular chromatin. Eligible patients were randomized (3:1) to the best available care including dexamethasone (R-BAC) or to BAC with twice-daily nebulized dornase alfa (R-BAC + DA) for seven days or until discharge. A 2:1 ratio of matched contemporary controls (CC-BAC) provided additional comparators. The primary endpoint was the improvement in C-reactive protein (CRP) over time, analyzed using a repeated-measures mixed model, adjusted for baseline factors. We recruited 39 evaluable participants: 30 randomized to dornase alfa (R-BAC +DA), 9 randomized to BAC (R-BAC), and included 60 CC-BAC participants. Dornase alfa was well tolerated and reduced CRP by 33% compared to the combined BAC groups (T-BAC). Least squares (LS) mean post-dexamethasone CRP fell from 101.9 mg/L to 23.23 mg/L in R-BAC +DA participants versus a 99.5 mg/L to 34.82 mg/L reduction in the T-BAC group at 7 days; p=0.01. The anti-inflammatory effect of dornase alfa was further confirmed with subgroup and sensitivity analyses on randomised participants only, mitigating potential biases associated with the use of CC-BAC participants. Dornase alfa increased live discharge rates by 63% (HR 1.63, 95% CI 1.01-2.61, p=0.03), increased lymphocyte counts (LS mean: 1.08 vs 0.87, p=0.02) and reduced circulating cf-DNA and the coagulopathy marker D-dimer (LS mean: 570.78 vs 1656.96 μg/mL, p=0.004). Dornase alfa reduces pathogenic inflammation in COVID-19 pneumonia, demonstrating the benefit of cost-effective therapies that target extracellular chromatin. LifeArc, Breathing Matters, The Francis Crick Institute (CRUK, Medical Research Council, Wellcome Trust). NCT04359654.