Diagnosis Of Coronavirus Disease 2019 Research Articles

525. Comparison of the acceptability and safety of molnupiravir in COVID-19 patients aged over and under 80 years

Abstract Background Molnupiravir is being widely used as a treatment for coronavirus disease 2019 (COVID-19); however, its acceptability and safety in older patients aged ≥ 80 years in real-world clinical practice is not well understood. Methods We conducted a single-centre retrospective study and assessed the outcome of patients with COVID-19 treated with molnupiravir according to the following criteria: (A) discontinuation rate of molnupiravir; (B) type, frequency, and severity of adverse events; (C) all-cause mortality within 30 days of the diagnosis of COVID-19. Results Forty-seven patients (46.1%) were aged ≥ 80 years (older patients) and 55 (53.9%) were aged < 80 years (younger patients). There were no significant differences in coexisting diseases and history of vaccination for COVID-19 between older and younger patients. Older patients were significantly more likely to have moderate disease (moderate 1 and 2) according to the Japanese Ministry of Health, Labour and Welfare classification than younger patients. During treatment, 8.5% of older patients and 1.8% of younger patients stopped taking molnupiravir, but the difference was not significant. Adverse events were observed in 39/102 (38.2%) patients. The most common adverse events were diarrhoea (9.8%), exacerbation of coexisting diseases (6.9%), bone marrow suppression (6.9%), liver dysfunction (5.9%), and loss of appetite (4.9%). Most adverse events were minor, ranging from grades 1 to 3. The all-cause mortality rate was 10.8%, and no molnupiravir-related deaths were observed. Conclusion Molnupiravir treatment is acceptable and safe in older patients with COVID-19 aged ≥ 80 years. Disclosures All Authors: No reported disclosures

Study on brain damage patterns of COVID-19 patients based on EEG signals

ObjectiveThe coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the SARA-CoV-2, characterized by high infectivity and incidence. Clinical data indicates that COVID-19 significantly damages patients’ perception, motor function, and cognitive function. However, the electrophysiological mechanism by which the disease affects the patient’s nervous system is not yet clear. Our aim is to investigate the abnormal levels of brain activity and changes in brain functional connectivity network in patients with COVID-19.MethodsWe compared and analyzed electroencephalography signal sample entropy, energy spectrum, and brain network characteristic parameters in the delta (1–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–30 Hz) bands of 15 patients with COVID-19 and 15 healthy controls at rest.ResultsAt rest, energy values of the four frequency bands in the frontal and temporal lobes of COVID-19 patients were significantly reduced. At the same time, the sample entropy value of the delta band in COVID-19 patients was significantly increased, while the value of the beta band was significantly decreased. However, the average value of the directed transfer function of patients did not show any abnormalities under the four frequency bands. Furthermore, node degree in the temporal lobe of patients was significantly increased, while the input degree of the frontal and temporal lobes was significantly decreased, and the output degree of the frontal and occipital lobes was significantly increased.ConclusionThe level of brain activity in COVID-19 patients at rest is reduced, and the brain functional network undergoes a rearrangement. These results preliminarily demonstrate that COVID-19 patients exhibit certain brain abnormalities during rest, it is feasible to explore the neurophysiological mechanism of COVID-19’s impact on the nervous system by using EEG signals, which can provide a certain technical basis for the subsequent diagnosis and evaluation of COVID-19 using artificial intelligence and the prevention of brain nervous system diseases after COVID-19 infection.

Summarizing Evidence of Associations of COVID-19 With a Future Diagnosis of Inflammatory Rheumatic and Musculoskeletal Diseases: A Rapid Review.

Musculoskeletal symptoms are commonly reported following acute COVID-19. It is unclear whether those with musculoskeletal symptoms subsequently develop inflammatory rheumatic musculoskeletal disease (iRMD). This review seeks to identify evidence for an association between acute COVID-19 and subsequent iRMD diagnosis. A rapid review of the literature using a systematic search of Medline, EMBASE and two COVID-19 databases was undertaken until August 2022. Case studies, case series, cross-sectional, case-control, and cohort studies reporting patients with an incident iRMD following COVID-19 were included. Title and abstract screening were conducted by one reviewer and full text screening by two reviewers. Data extraction and quality appraisal were by one reviewer, with a second verifying. Study-type specific critical appraisal tools were used. Results were narratively synthesized. A total of 80 studies were included (69 case reports, 10 case series and 1 cross-sectional study). Commonly reported iRMDs were "reactive arthropathies" (n=47), "inflammatory arthropathies unspecified" (n=18), rheumatoid arthritis (n=12) and systemic lupus erythematosus (n=11). The cross-sectional study reported 37% of those with COVID-19 developed "post COVID arthritis." Time from diagnosis of COVID-19 to iRMD presentation ranged from 0 to 120 days. Several mechanisms were proposed to explain the association between COVID-19 and iRMD development: autoimmune processes, aberrant inflammatory responses, colonization of joint spaces, direct damage from the severe acute respiratory syndrome coronavirus 2 virus and genetic predisposition. The level of evidence of the studies included in this review was low and the quality generally poor. Prospective observational studies are required to confirm associations and likely impact of post COVID-19 iRMDs at a population level.

A Comparison of the Epidemiological Characteristics Between Influenza and COVID-19 Patients: A Retrospective, Observational Cohort Study.

Background and objective It is crucial to make early differentiation between coronavirus disease 2019 (COVID-19) and seasonal influenza infections at the time of a patient's presentation to the emergency department (ED). In light of this, this study aimed to identify key epidemiological, initial laboratory, and radiological differences that would enable early recognition during co-circulation. Methods This was a retrospective, observational cohort study. All adult patients presenting to our ED at the Watford General Hospital, UK, with a laboratory-confirmed diagnosis of COVID-19 (2019/20) or influenza (2018/19) infection were included in this study. Demographic, laboratory, and radiological data were collected. Binary logistic regression was employed to determinefeatures associated with COVID-19 infection rather than influenza. Results Chest radiographs suggestive of viral pneumonitis and older age (≥80 years) were associated with increased odds of having COVID-19 [odds ratio (OR): 47.00, 95% confidence interval (CI): 21.63-102.13and OR: 64.85, 95% CI: 19.96-210.69respectively]. Low eosinophils (<0.02 x 109/L) were found to increasethe odds of COVID-19 (OR: 2.12, 95% CI: 1.44-3.10, p<0.001). Conclusions Gaining awareness about the epidemiological, biological, and radiologic presentation of influenza-like illness can be useful for clinicians in ED to differentiate between COVID-19 and influenza. This study showed that older age, eosinopenia, and radiographic evidence of viral pneumonitis significantly increase the odds of having COVID-19 compared to influenza. Further research is needed to determine if these findings are affected by acquired or natural immunity.

Association between sequelae of COVID-19 with periodontal disease and obesity: A cross-sectional study.

To assess the sequelae of coronavirus disease 2019 (COVID-19) and associated factors, such as obesity and periodontitis in adults. The study included 128 individuals aged ≥35 years with a history of a diagnosis of COVID-19 through real-time polymerase chain reaction (RT-PCR), from Pelotas, Brazil. Self-report sequelae from COVID-19 were defined as the primary outcome. A questionnaire containing sociodemographic, medical, behavioral and self-report of sequelae of COVID-19 was applied. A complete periodontal clinical examination was performed. Weight and height were assessed. Uni-, bi- and multivariate analyses were performed using Poisson regression with robust variance. Additional analyses were performed considering obesity as a subgroup. When considering the whole sample, no statistically significant associations between sequelae of COVID-19 with periodontitis (prevalence ratio [PR]:1.14;95% confidence interval [95%CI]: 0.80-1.61) and obesity (0.93 [0.68-1.26]) were identified. In the subgroup analysis, considering only individuals with obesity, those diagnosed with generalized periodontitis had 86% higher probability to have sequelae of COVID-19 when compared to individuals with periodontal health or localized periodontitis. However, when only those without obesity were considered, no significant association with periodontal status was detected (0.82 [0.55-1.23). No significant association with periodontal status were observed when the severity of sequelae (no sequelae, 1 sequela, and >1 sequela) were considered (p>0.05). Individuals diagnosed with obesity and periodontitis have a higher PR of reporting sequelae from COVID-19 compared to individuals with only obesity.

Utility of Bronchoalveolar Lavage for the Diagnosis and Management of COVID-19 in Patients With Cancer.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) on nasopharyngeal swab (NPS), remains the most reliable and practical test to diagnose coronavirus disease 2019 (COVID-19). Current literature is sparse regarding the rates of discordance between NPS and bronchoalveolar lavage (BAL) in patients with cancer. We conducted a retrospective cohort study of adult patients with cancer who had BAL samples tested for SARS-CoV-2 at a comprehensive cancer center. Patients without NPS PCR for SARS-CoV-2 before BAL were excluded. In a cohort of 345 patients, 12% and 17% tested positive for SARS-CoV-2 on NPS and BAL, respectively. There was a 6.3% NPS-/BAL+ discordance rate and a 9.5% NPS+/BAL- discordance rate. Patients with lymphoma (adjusted odds ratio [aOR] = 4.06; P = .007) and Hispanic patients (aOR = 3.76; P = .009) were more likely to have NPS-/BAL+ discordance on multivariate analysis. Among patients with NPS- /BAL- for SARS-CoV-2, an alternate infectious (23%) and a noninfectious etiology (16%) were identified in BAL. Our discordance rates between NPS and BAL were sufficient to recommend BAL in certain patients with cancer with a high clinical suspicion of COVID-19. BAL has value in identifying alternative etiologies of illness in patients with suspected or confirmed COVID-19.

The relation between vaccination status and referral to a consultation–liaison psychiatry service for hospitalized patients with COVID-19

BackgroundPrevious studies have shown that patients with Coronavirus Disease 2019 (COVID-19) are likely to be affected by delirium and other psychiatric complications. We aimed to evaluate the relation between COVID-19 vaccination status and referral of patients hospitalized with COVID-19 for consultation–liaison psychiatry services.MethodFrom the medical records used for this retrospective, single hospital-based study, 576 patients were identified who were over 18 years-of-age and hospitalized with a diagnosis of COVID-19 between March 2020 and March 2022. The data of 531 for whom the vaccine history was obtained from the medical records were available for analysis: 455 without and 76 with referral to consultation–liaison psychiatry. A history of COVID-19 vaccination at least two times was used in the analysis of the odds for referral to liaison psychiatric consultation: 95% confidence interval (CI) in multivariable logistic regression. The adjustment factors included sex, age, body mass index (BMI), severity of COVID-19, C-reactive protein level, medical history, and therapeutic factors such as the use of remdesivir, steroids, or mechanical ventilation.ResultsThe prevalence of psychiatric consultation was 14.3%. Patients without vaccination had a 7-times greater OR (95%CI:2.08–23.58) than vaccinated patients for a referral for consultation–liaison psychiatry services after adjusting for confounding factors.ConclusionNon-vaccination was associated with a greater likelihood of referral for consultation–liaison psychiatry service among these hospitalized Japanese patients with COVID-19, even after adjusting for clinical and therapeutic factors. It is possible that vaccination greatly lessens the need for the referral of COVID-19 patients for consultation–liaison psychiatry services.

COVID-19 Detection via Ultra-Low-Dose X-ray Images Enabled by Deep Learning.

The detection of Coronavirus disease 2019 (COVID-19) is crucial for controlling the spread of the virus. Current research utilizes X-ray imaging and artificial intelligence for COVID-19 diagnosis. However, conventional X-ray scans expose patients to excessive radiation, rendering repeated examinations impractical. Ultra-low-dose X-ray imaging technology enables rapid and accurate COVID-19 detection with minimal additional radiation exposure. In this retrospective cohort study, ULTRA-X-COVID, a deep neural network specifically designed for automatic detection of COVID-19 infections using ultra-low-dose X-ray images, is presented. The study included a multinational and multicenter dataset consisting of 30,882 X-ray images obtained from approximately 16,600 patients across 51 countries. It is important to note that there was no overlap between the training and test sets. The data analysis was conducted from 1 April 2020 to 1 January 2022. To evaluate the effectiveness of the model, various metrics such as the area under the receiver operating characteristic curve, receiver operating characteristic, accuracy, specificity, and F1 score were utilized. In the test set, the model demonstrated an AUC of 0.968 (95% CI, 0.956-0.983), accuracy of 94.3%, specificity of 88.9%, and F1 score of 99.0%. Notably, the ULTRA-X-COVID model demonstrated a performance comparable to conventional X-ray doses, with a prediction time of only 0.1 s per image. These findings suggest that the ULTRA-X-COVID model can effectively identify COVID-19 cases using ultra-low-dose X-ray scans, providing a novel alternative for COVID-19 detection. Moreover, the model exhibits potential adaptability for diagnoses of various other diseases.

Longitudinal Analysis of Antibody Response Following SARS-CoV-2 Infection Depending on Disease Severity: A Prospective Cohort Study.

Severe coronavirus disease 19 (COVID-19) is characterized by a dysregulated inflammatory response, with humoral immunity playing a central role in the disease course. The objective of this study was to assess the immune response and the effects of vaccination in recovered individuals with variable disease severity up to one year following natural infection. A prospective cohort study was conducted including patients with laboratory-confirmed COVID-19. Disease severity was classified as mild, moderate, and severe based on clinical presentation and outcomes. Anti-RBD (receptor binding domain) and neutralizing antibodies were evaluated at multiple timepoints during the first year after COVID-19 diagnosis. A total of 106 patients were included; of them, 28 were diagnosed with mild, 38 with moderate, and 40 with severe disease. At least one vaccine dose was administered in 58 individuals during the follow-up. Participants with mild disease presented significantly lower anti-RBD and neutralizing antibodies compared to those with moderate and severe disease up to the 3rd and 6th months after the infection, respectively. After adjusting for covariates, in the third month, severe COVID-19 was associated with significantly higher anti-RBD (β: 563.09; 95% confidence intervals (CI): 257.02 to 869.17) and neutralizing (β: 21.47; 95% CI: 12.04 to 30.90) antibodies. Among vaccinated individuals, at the 12th month, a history of moderate disease was associated with significantly higher anti-RBD levels (β: 5615.19; 95% CI: 657.92 to 10,572.46). Severe COVID-19 is associated with higher anti-RBD and neutralizing antibodies up to 6 months after the infection. Vaccination of recovered patients is associated with a remarkable augmentation of antibody titers up to one year after COVID-19 diagnosis, regardless of disease severity.

Lower ventricular and atrial strain in patients who recovered from COVID-19 assessed by cardiovascular magnetic resonance feature tracking.

One of the most common complications of coronavirus disease 2019 (COVID-19) is myocardial injury, and although its cause is unclear, it can alter the heart's contractility. This study aimed to characterize the ventricular and atrial strain in patients who recovered from COVID-19 using cardiovascular magnetic resonance feature-tracking (CMR-FT). In this single-center study, we assessed left ventricle (LV) and right ventricular (RV) global circumferential strain (GCS), global longitudinal strain (GLS), global radial strain (GRS), left atrial (LA) and right atrial (RA) longitudinal strain (LS) parameters by CMR-FT. The student's t-test and Wilcoxon rank-sum test were used to compare the variables. We compared seventy-two patients who recovered from COVID-19 (49 ± 16 years) to fifty-four controls (49 ± 12 years, p = 0.752). The patients received a CMR examination 48 (34 to 165) days after the COVID-19 diagnosis. 28% had LGE. Both groups had normal LV systolic function. Strain parameters were significantly lower in the COVID-19 survivors than in controls. Patients who recovered from COVID-19 exhibited significantly lower strain in the left ventricle (through LVGCS, LVGLS, LVGRS), right ventricle (through RVGLS and RVGRS), left atrium (through LALS), and right atrium (through RALS) than controls.

Changes in Site of Death Among Older Adults Without a COVID-19 Diagnosis During the COVID-19 Pandemic

BackgroundUnderstanding how the coronavirus disease 2019 (COVID-19) pandemic affected site of death—an important patient-centered outcome related to end-of-life care—would inform healthcare system resiliency in future public health emergencies.ObjectiveTo evaluate the changes in site of death during the COVID-19 pandemic among older adults without a COVID-19 diagnosis.DesignUsing a quasi-experimental difference-in-differences method, we estimated net changes in site of death during the pandemic period (March–December 2020) from the pre-pandemic period (January–February 2020), using data on the same months in prior years (2016–2019) as the control.ParticipantsA 20% sample of Medicare Fee-for-Service beneficiaries aged 66 years and older who died in 2016–2020. We excluded beneficiaries with a hospital diagnosis of COVID-19.Main MeasuresWe assessed each of the following sites of death separately: (1) home or community; (2) acute care hospital; and (3) nursing home.Key ResultsWe included 1,133,273 beneficiaries without a hospital diagnosis of COVID-19. We found that the proportion of Medicare beneficiaries who died at home or in the community setting increased (difference-in-differences [DID] estimate, + 3.1 percentage points [pp]; 95% CI, + 2.6 to + 3.6 pp; P < 0.001) and the proportion of beneficiaries who died (without COVID-19 diagnosis) in an acute care hospital decreased (− 0.8 pp; 95% CI, − 1.2 to − 0.4 pp; P < 0.001) during the pandemic. We found no evidence that the proportion of deaths in nursing homes changed during the pandemic.ConclusionsUsing national data on older adults without a COVID-19 diagnosis, we found that site of death shifted toward home or community settings during the COVID-19 pandemic. Our findings may inform clinicians and policymakers in supporting end-of-life care during future public health emergencies.

Comparing the effect of obesity on major adverse cardiovascular events in patients hospitalized with coronavirus disease-2019 (COVID-19): insights from the national inpatient sample (NIS) database

Abstract Introduction Recent studies have shown an ‘obesity paradox,’ which refers to improved hospital outcomes and prognosis in obese individuals when compared to their non-obese counterparts. This paradox is evident when myocardial infarction (MI), venous thromboembolism (VTE), and cardiovascular mortality are considered. There is limited information extrapolated from large inpatient databases describing inpatient hospital outcomes of patients with obesity and concomitant COVID-19. Purpose To determine the association of obesity with inpatient mortality of acute (MI), cerebrovascular accidents (CVA) and cardiovascular death in patients with COVID-19 using the NIS database. Methods The NIS database for calendar year 2020 was queried to identify adult hospitalizations with a primary diagnosis of COVID-19 and a secondary diagnosis of obesity. Cases were identified using International Classification of Diseases – 10 Clinical Modification (ICD-10-CM) codes. The primary outcome was inpatient mortality; secondary outcomes were length of stay (LOS), total hospital charge (THC), and inpatient complications. Linear, univariate, and multivariate logistic regression were used to analyze the outcomes and adjust for confounders. Results A total of 1,050,045 hospitalizations for COVID-19 were identified, 292,800 (27.9%) of which had the co-diagnosis of obesity. Out of the identified hospitalizations with COVID-19 and obesity, 29,290 (10%) died. After multivariate adjustment for confounding variables, obesity was associated with increased inpatient mortality (adjusted odds [aOR] 1.37; 95% confidence interval [CI] 1.32-1.42, p &amp;lt; 0.001), while CVA and acute MI were negatively associated with obesity (aOR 0.81; CI 0.68-0.97, p = 0.023 and aOR 0.92; CI 0.86-0.99, p = 0.026, respectively). Additionally, obesity was associated with multiple inpatient complications, including but not limited to: sepsis (aOR 1.44; CI 1.38-1.51, p &amp;lt; 0.001); acute respiratory failure (aOR 1.46; CI 1.43-1.50, p &amp;lt; 0.001), need for intubation (aOR 1.66; CI 1.60-1.73, p &amp;lt; 0.001), need for mechanical ventilation (aOR 1.69; CI 1.62-1.75, p &amp;lt; 0.001); cardiac arrest (aOR 1.32; CI 1.23-1.42, p &amp;lt; 0.001); and need for cardiopulmonary resuscitation (aOR 1.37; CI 1.26-1.50, p &amp;lt; 0.001). Conclusion The findings of this study are inconsistent with the obesity paradox. Obese patients hospitalized with COVID-19 had an increased association of mortality and inpatient complications; however, there was a negative association between obesity and CVA and acute MI.

Abstract 14906: Incidence and Impact of Takotsubo Syndrome in Hospitalized COVID-19 Patients

Background: Takotsubo syndrome (TTS) has been reported in coronavirus disease-2019 (COVID-19) patients, although minimal data are available. Objectives: We assessed the incidence and impact of TTS on hospitalized COVID-19 patients. Methods: We conducted a retrospective cohort study using ICD-10 to identify patients with a primary diagnosis of COVID-19 with or without TTS in the National Inpatient Sample 2020 database. We compared outcomes between both groups after propensity score matching for patient and hospital demographics and comorbidities. Results: A total of 211,448 patients with a primary diagnosis of COVID-19 were identified. Of these, 171 (0.08%) had a secondary diagnosis of TTS. Before matching, COVID-19 patients with TTS, compared with those without TTS, were older (68.95 vs 64.26 years) and more likely to be female (64.3% vs 47.2%) and to have anxiety (24.6% vs 12.8), depression (17.5% vs 11.4%), and COPD (24.6% vs 14.7%) (all p&lt;0.05). The TTS group had worse outcomes in death (30.4% vs 11.1%), cardiac arrest (7.6% vs 2.1%), cardiogenic shock (12.9% vs 0.4%), length of stay (LOS, 10.7 vs 7.5 days), and total charges ($152,685 vs $78,468), respectively (all p&lt; 0.001). After matching, the TTS group (n=170), compared with the non-TTS group (n=508), had a higher incidence of inpatient mortality (30% vs 14%, p&lt;0.001), cardiac arrest (7.6% vs 2.8%, p=0.009), and cardiogenic shock (12.4% vs 0.4%, p&lt;0.001), a longer LOS (10.7 vs 7.6 days, p&lt;0.001), and higher total charges ($152,943 vs $79,523, p&lt;0.001). Conclusions: TTS is a rare but severe in-hospital complication in COVID-19 patients.

Post-acute sequelae of COVID-19 in solid organ transplant recipients.

Post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), defined as prolonged symptoms following an episode of COVID-19, is not well-characterized in solid organ transplant recipients (SOTR). In this study, we aimed to assess the prevalence of PASC in SOTR, its descriptive characteristics, and associated risk factors. We retrospectively identified SOTRs with acute COVID-19 between June 1, 2020 and April 15, 2022, and abstracted demographic and medical history, characteristics of acute COVID-19 illness, and COVID-19 vaccination status. We defined PASC as ongoing/new symptoms present at 6weeks or longer following acute COVID-19 diagnosis. Among 208 SOTRs with acute COVID-19, 72 (35%) developed PASC. Common symptoms were respiratory symptoms (67%), headache (40%), and difficulty concentrating (10%). Severe acute COVID-19 disease and presence of respiratory symptoms were associated with higher odds of PASC in multivariable analyses, while receipt of at least one COVID-19 vaccination prior to transplantation was protective. We found that PASC occurs in about a third of SOTRs with acute COVID-19 and has similar symptoms as described previously in immunocompetent hosts. Pre-transplant vaccination may be protective. Further prospective multicenter studies are needed.

Biochemical, Serological and Immunological Tests for Diagnosis of Coronavirus Disease 2019 (COVID-19) Patients: A Comprehensive Systematic Review and Meta-analysis.

Recent studies have suggested the role of primary laboratory tests in addition to clinical symptoms for patients suspected to have coronavirus disease 2019 (COVID-19), which play a significant role in the diagnosis of COVID-19. However, the results of these studies are contradictory. The present study was conducted to evaluate biochemical, serological, and immunological tests for the diagnosis of COVID-19 patients. This study was presented in accordance with the PRISMA protocol. This protocol is registered with the code CRD42019145410 in PROSPERO. We conducted a comprehensive literature search in databases, including Web of Science, PubMed/Medline, CINAHL Scopus, Cochrane Library, EMBASE, Science Direct, and EBSCO to find citations from the beginning of January 2019 until the beginning of April 2020 without any restrictions. Finally, 51 studies, including 5,490 COVID-19 patients, were included in the present metaanalysis. The prevalence of different factors observed in laboratory findings was as follows: the prevalence of lymphopenia in patients with COVID-19 accounted for 51.6% (95% CI: 44.0-59.1), elevated C-reactive protein (CRP) was 63.6% (95% CI: 57.0-69.8), elevated erythrocyte sedimentation rate (ESR) was 62.5% (95% CI: 50.1-73.5), elevated tumor necrosis factor alpha (TNFα) was 28.7% (95% CI: 9.0-62.1), elevated serum amyloid-A level was 74.7% (95% CI: 50.0-89.7), elevated procalcitonin level was 72.6% (95% CI: 58.1-83.5), elevated interleukin-6 level was 59.9% (95% CI: 48.2-70.5), reduced CD3 level was 68.3% (95% CI: 50.1-82.2), reduced CD4 level was 62.0% (95% CI: 51.1- 71.6), elevated lactate dehydrogenase (LDH) level accounted for 53.1% (95% CI: 43.6-62.4), elevated brain natriuretic peptide (BNP) accounted for 48.9% (95% CI: 30.4-67.7), reduced albumin and reduced pre-albumin levels in patients with COVID-19 were estimated to be 54.7% (95% CI: 38.1-70.2) and 49.0% (95% CI: 26.6-71.8), and D-dimer level was 44.9% (95% CI: 31.0-59.6). The results show lymphopenia, elevated ESR level, elevated CRP level, elevated serum amyloid-A, elevated TNFα, elevated procalcitonin level, elevated interleukin-6 level, reduced CD3, reduced CD4, elevated BNP, elevated LDH, reduced albumin, reduced pre-albumin, and elevated Ddimer levels as the most common findings at the time of admission.

The fourth COVID-19 vaccine dose increased the neutralizing antibody response against the SARS-CoV-2 Omicron (B.1.1.529) variant in a diverse Brazilian population.

Most of the original immunization regimens against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were composed of two doses, followed by a subsequent third booster dose to control the Omicron variant and hence coronavirus disease 2019 (COVID-19). However, most data generated regarding the fourth dose were not based on the general population. Therefore, this study aimed to verify the effect of the fourth COVID-19 vaccine dose in a diverse Brazilian population. This retrospective observational study was conducted between May and September 2022. We gathered data on the vaccine regimens and COVID-19 serologic status from 266 healthy volunteers who received three or four vaccine doses, as well as COVID-19 diagnosis and viral genome sequencing from 457 patients with flu-like symptoms. In addition, we conducted immunoinformatic analysis to assess the conserved epitopes in the locally circulating viruses. We showed that the fourth dose did not increase the serum levels of antiviral antibodies, as measured by enzyme-linked immunosorbent assay. However, it significantly increased neutralizing antibody (NAb) titers against the Omicron variant. All viral sequences generated in this study were Omicron subvariants, mainly B.A.5.1. Notably, most NAb epitopes present in the wild-type SARS-CoV-2 were not detected among the circulating Omicron subvariants. None of the volunteers who received the third or fourth doses presented COVID-19 for at least 1 year before the study period. Altogether, these results indicate that the fourth vaccine dose increases the serum levels of NAbs that recognize highly conserved epitopes in Omicron subvariants.IMPORTANCESeveral additional COVID-19 vaccine doses were administered in the Brazilian population to prevent the disease caused by the B.1.1.529 (Omicron) variant. The efficacy of a third dose as a booster is already well described. However, it is important to clarify the humoral immune response gain induced by a fourth dose. In this study, we evaluate the effect of the fourth COVID-19 vaccine dose in a diverse Brazilian population, considering a real-life context. Our study reveals that the fourth dose of the COVID-19 vaccine increased the neutralizing antibody response against SARS-CoV-2 Omicron and significantly contributed in the reduction of the disease caused by this variant.

Sex-Specific Total Testosterone and Dehydroepiandrosterone Sulfate Status in Noncritically Ill Hospitalized Patients with Coronavirus Disease 2019: A Cross-Sectional Study.

In individuals with coronavirus disease 2019 (COVID-19), male subjects have consistently been linked to poor severity and prognosis. Data on sex hormones in non-critical COVID-19-infected patients are scarce. The aim of this study was to assess the status of total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS) among noncritical patients with COVID-19 according to sex and their associations with clinical and biochemical features. This cross-sectional observational study was done in the COVID-19 unit of a University hospital during the period of September 2021 to February 2022 among 91 adults (18-65 years) with reverse transcriptase- polymerase chain reaction confirmed noncritical COVID-19 patients. Blood was drawn by venipuncture before receiving steroids between 07:00 to 09:00 a.m. in a fasting state to measure serum TT and DHEAS by chemiluminescent microparticle immunoassay. Diagnosis and classification of COVID-19 were done according to World Health Organization's interim guidance. Age- and sex-specific laboratory reference values were used to classify the TT and DHEAS status of the patients. Only three males (8.1%) had low TT and the rest had normal TT. On the other hand, 15 (27.8%) of the females had high TT with normal levels in the rest. Similarly, 11 (29.7%) males had low DHEAS. Females had low, normal, and high DHEAS in four (7.4%), 48 (88.9%), and two (3.7%) cases respectively. Males with moderate severity of COVID-19 had significantly lower DHEAS (post hoc P=0.038) than the mild group. Both TT (P=0.008) and DHEAS (P=0.023) significantly correlated with neutrophils/lymphocytes ratio and only DHEAS with platelets/lymphocytes ratio (P=0.044) in males. In females, TT significantly correlated with serum sodium (P=0.034). In noncritical COVID-19 patients, substantial gender variations in TT and DHEAS were detected and correlated with severity markers in males.

Acute Corneal Hydrops in Keratoconus Coinciding With COVID-19 Infection.

To the Editor: Acute corneal hydrops (AH), characterized by corneal stromal edema after a Descemet membrane rupture that allows aqueous humor entry, is observed in cases of keratoconus. Patients typically present with rapidly deteriorating visual acuity, photophobia, and pain. A timely diagnosis and management are essential to ruling out other vision-threatening pathologies such as corneal edema, infectious keratitis, uveitis, Fuchs endothelial dystrophy, postoperative edema, and acute transplant rejection. Here we describe a case of AH in a patient with keratoconus coinciding with coronavirus disease 2019 (COVID-19) infection and emphasize the importance of patient education in the context-restricted face-to-face consultations. A 20-year-old healthy man was evaluated regularly every 3 months for keratoconus using visual acuity and refraction assessments and anterior segment optical coherence tomography imaging. He wore corneal rigid gas-permeable contact lenses in both eyes. He also had a mild ocular allergy but no atopy or habit of eye-rubbing. There was no family history of keratoconus. A year earlier, he had an episode of AH in his left eye. While his left eye stabilized after pressure patching, the keratoconus progressed in his right eye. Examination findings at his last visit before the COVID-19 diagnosis included: corrected distance visual acuity with a gas-permeable contact lens of 20/30 (right) and 20/16 (left), anterior keratometry of 66.4 D (right) and 43.5 D (left), the thinnest corneal thickness of 264 mm (right) and 468 mm (left), and posterior “best-fit sphere” 9-mm radius values of 4.88 (right) and 6.46 mm (left). Approximately 2 months after the last follow-up, he developed flu-like symptoms (sore throat and fever) and was diagnosed the next day with COVID-19 on polymerase chain reaction. Two days after symptom onset, he noticed sudden deterioration of vision in his right eye and called our hospital. The cornea specialist in the ophthalmology department made a tentative phone diagnosis of AH based on his ocular history and instructed him to apply a pressure patch with ophthalmic ointment. He was examined at our hospital after 10 days of quarantine. The corrected distance visual acuity of the right eye was 20/2000, while a slitlamp examination revealed corneal protrusion and marked corneal epithelial as well as stromal edema in the right eye. Fluorescein corneal observation showed no epithelial abnormality, and a definitive AH diagnosis was made. Optical coherence tomography imaging revealed a break in Descemet membrane with overlying corneal edema (Supplemental Digital Content Fig. 1, https://links.lww.com/APJO/A179). No abnormality was noted in the left eye. He had received the second COVID-19 vaccine dose 1 month before the viral infection and reported experiencing no vaccine-related complications. On examination a month later, the AH in the right eye had remarkably improved. Various ophthalmic management and care delivery experiences have been reported during the COVID-19 pandemic. Perspectives in corneal crosslinking were reported relating to keratoconus in particular.1,2 To the best of our knowledge, our case is the first of AH with concomitant keratoconus and COVID-19 infection, although it was not possible to demonstrate a clear association among them. A previous history of AH in either eye is a predisposing risk factor for AH.3 This case underscores the importance of informing patients of their disease status and the need to undergo regular examinations. However, patients with COVID-19 may not be able to receive a timely ophthalmic examination. This patient was distressed until the postquarantine ophthalmic examination was performed; however, his previous experience with AH including successful pressure patching was helpful for the clinician and patient, who was better able to understand the extent of his condition and follow the provided instructions. In the absence of a clinical history of keratoconus, effectively managing AH before a face-to-face examination could be performed would have been challenging. Here are summary points of consideration when educating a patient with an acute event during a pandemic setting: Recognize the patient’s distress due to being in isolation during the acute event. Provide clear information about the disease and instructions for its independent management during quarantine. Strict hand hygiene should be thoroughly practiced while applying the pressure patch and patients should keep unwashed hands away from their face at times. Remote management may require conservative management methods. This requires careful consideration, particularly in acute ophthalmic cases. Although keratoconus was previously considered a noninflammatory ectatic corneal disease, recent evidence shows a relationship between its pathogenesis and chronic inflammatory events.4,5 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is known to cause a proinflammatory state.6 There are several reports of corneal graft rejection in patients infected with COVID-19.6–8 Large population-based case-control studies are needed to investigate the possible association between AH in keratoconus and the SARS-CoV-2 cytokine response. Shizuka Koh, MD, PhD*† Takeshi Soma, MD, PhD† Vishal Jhanji, MD‡ Kohji Nishida, MD, PhD†

MultiCOVID: a multi modal deep learning approach for COVID-19 diagnosis

The rapid spread of the severe acute respiratory syndrome coronavirus 2 led to a global overextension of healthcare. Both Chest X-rays (CXR) and blood test have been demonstrated to have predictive value on Coronavirus Disease 2019 (COVID-19) diagnosis on different prevalence scenarios. With the objective of improving and accelerating the diagnosis of COVID-19, a multi modal prediction algorithm (MultiCOVID) based on CXR and blood test was developed, to discriminate between COVID-19, Heart Failure and Non-COVID Pneumonia and healthy (Control) patients. This retrospective single-center study includes CXR and blood test obtained between January 2017 and May 2020. Multi modal prediction models were generated using opensource DL algorithms. Performance of the MultiCOVID algorithm was compared with interpretations from five experienced thoracic radiologists on 300 random test images using the McNemar–Bowker test. A total of 8578 samples from 6123 patients (mean age 66 ± 18 years of standard deviation, 3523 men) were evaluated across datasets. For the entire test set, the overall accuracy of MultiCOVID was 84%, with a mean AUC of 0.92 (0.89–0.94). For 300 random test images, overall accuracy of MultiCOVID was significantly higher (69.6%) compared with individual radiologists (range, 43.7–58.7%) and the consensus of all five radiologists (59.3%, P < .001). Overall, we have developed a multimodal deep learning algorithm, MultiCOVID, that discriminates among COVID-19, heart failure, non-COVID pneumonia and healthy patients using both CXR and blood test with a significantly better performance than experienced thoracic radiologists.

Frequency of Lymphopenia in Infants with COVID-19: Vaccination Dilemma

Abstract Objective Although coronavirus disease 2019 (COVID-19) is mainly a respiratory system disease, many hematological abnormalities have been reported. Due to the application of primary immunization in infancy, our study aimed to examine the relationship between lymphopenia frequency and duration of lymphopenia in infants with COVID-19. Methods The files of infants hospitalized with the diagnosis of COVID-19 in the Pediatric Pandemic Service of Istanbul Medical Faculty between January 2020 and October 2022 were evaluated retrospectively. Demographic characteristics, leukocyte, lymphocyte count, comorbidity, hospitalization, and lymphopenia recovery time were recorded. Results In this study, 93 infants with COVID-19 were included. Lymphopenia was detected in 62 of these patients (n = 62/93, 66.7%). The 47.3% of the patients were female (n = 44) and the mean age was 6 ± 3.42 months. Comorbidities were detected in the 33% of the patients. Lymphopenia resolved in an average of 11 days. While the mean hospitalization period of patients with lymphopenia was 3.6 ± 2.9 (minimum: 1 and maximum: 15) days, the mean hospitalization period of patients without lymphopenia was 2.5 days. Leukopenia (p: 0.014) and lymphopenia (p: 0.005) were more common in infants with chronic disease. Similarly, the duration of hospitalization and recovery from lymphopenia were statistically significantly longer (p: 0.016). A statistically significant correlation was found between the duration of lymphopenia recovery and the duration of hospitalization (p: 0.001). Conclusion Although we found lymphopenia as a common finding in infancy in our study, it was not observed frequently enough to require the postponement of the vaccination program due to its short duration. Vaccination should not be delayed due to lymphopenia in infants with COVID-19 to avoid a missed opportunity for vaccination.