Onset Of Coronavirus Disease 2019 Symptoms Research Articles

Detection of SARS-CoV-2-specific antibodies via rapid diagnostic immunoassays in COVID-19 patients

BackgroundEfficient monitoring and control of coronavirus disease 2019 (COVID-19) require access to diagnostic tests, and serological diagnostic testing is desirable. In the current study, antibodies were investigated in patients recently diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsCross-sectional data were obtained from 245 patients in whom SARS-CoV-2 infection had been confirmed via real-time reverse transcriptase-polymerase chain reaction between March and October 2020. Serum samples were acquired between 2 and 60 days following the onset of COVID-19 symptoms or the first detection of SARS-CoV-2 in asymptomatic patients. All specimens were tested simultaneously using an IgM/IgG rapid diagnostic test (RDT), IgG nucleocapsid protein-based chemiluminescent microparticle immunoassay (CMIA), IgG, and IgA spike protein-based enzyme-linked immunosorbent assays (ELISAs). Blood donor samples obtained in 2018 were used as negative controls.ResultsThe sensitivity and specificity of the RDT IgG were compared with the IgG immunoassays as standards. The RDT IgG exhibited 97.5% sensitivity and 89.4% specificity compared with a CMIA IgG, 98.4% sensitivity, and 78.8% specificity compared with an ELISA IgG. IgM, IgG, and IgA seropositivity rates were low between 1 and 2 weeks after COVID-19 symptom onset or the detection of SARS-CoV-2 RNA. IgM seropositivity rate began decreasing after 4 weeks, whereas IgG and IgA seropositivity rate remained at appreciable levels over the 8-week study period. No cross-reactivity with seasonal coronaviruses was detected.ConclusionsIgG RDT alone or combined with molecular diagnostic tests may be useful for identifying recent SARS-CoV-2 infection.

Abstract P89: Covid-19 and Ischemic Stroke: A Systematic Review and Meta-Summary of the Literature

Background: Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. Objectives: We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. Methods: A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. Results: A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean D-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). Conclusion: We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated D-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.

Donor tolerability of convalescent plasma donation.

BackgroundSince early 2020, convalescent plasma has been widely used for treating coronavirus disease 2019 (COVID‐19). There is limited information regarding donor tolerability of convalescent plasma donation. In this study, we evaluated the short‐term donor tolerability of convalescent plasma donation.MethodsA prospective study of 309 convalescent plasma donation related adverse events were conducted at Wuhan Blood Center of China, from February 12 to April 1, 2020. Additionally, up to 28‐day post‐donation follow‐ups were performed on the donors.ResultsSixteen (5.2%) adverse events were reported in 309 donations. All of these were mild vasovagal without loss of consciousness. The frequency of adverse reactions was higher in donors with a per donation volume of >8 mL/kg body weight or ≥ 600 mL, <100 mm Hg in pre‐donation systolic blood pressure, or less than 28 days from the onset of COVID‐19 symptoms. There was no correlation to donation history, weight, sex, ABO blood type, pre‐donation diastolic blood pressure, pulse, or hemoglobin.ConclusionThe donation of convalescent plasma is generally safe. Mitigation of risk factors associated with adverse events can further enhance donor tolerability of convalescent plasma donation.

High Systolic Blood Pressure at Hospital Admission Is an Important Risk Factor in Models Predicting Outcome of COVID-19 Patients.

BACKGROUNDThe risk that coronavirus disease 2019 (COVID-19) patients develop critical illness that can be fatal depends on their age and immune status and may also be affected by comorbidities like hypertension. The goal of this study was to develop models that predict outcome using parameters collected at admission to the hospital.METHODS AND RESULTSThis is a retrospective single-center cohort study of COVID-19 patients at the Seventh Hospital of Wuhan City, China. Forty-three demographic, clinical, and laboratory parameters collected at admission plus discharge/death status, days from COVID-19 symptoms onset, and days of hospitalization were analyzed. From 157 patients, 120 were discharged and 37 died. Pearson correlations showed that hypertension and systolic blood pressure (SBP) were associated with death and respiratory distress parameters. A penalized logistic regression model efficiently predicts the probability of death with 13 of 43 variables. A regularized Cox regression model predicts the probability of survival with 7 of above 13 variables. SBP but not hypertension was a covariate in both mortality and survival prediction models. SBP was elevated in deceased compared with discharged COVID-19 patients.CONCLUSIONSUsing an unbiased approach, we developed models predicting outcome of COVID-19 patients based on data available at hospital admission. This can contribute to evidence-based risk prediction and appropriate decision-making at hospital triage to provide the most appropriate care and ensure the best patient outcome. High SBP, a cause of end-organ damage and an important comorbid factor, was identified as a covariate in both mortality and survival prediction models.

The Impact of Coronavirus Disease 2019 (COVID-19) among Immune Compromised Patients in Augusta Victoria Hospital AVH-2021

Background: Coronavirus disease 2019 which is officially known as COVID-19 belongs to family viruses. COVID-19 manifestations vary among affected people. These symptoms may become more serious among patients suffering from chronic disease and those who are on treatment which may af-fect their defense mechanism or immune-compromised patients who become more vulnerable to complications of COVID-19, and at high risk for morbidity and mortality with any bacterial or viral illness. Method: A retrospective, non-experimental research design was applied with a quantitative approach among patients with COVID-19 who were admitted to COVID-19 department at AVH with a total of 72 patients. Data were extracted from a patients’ elec-tronic medical record. Results: During COVID-19 outbreak 72 patients were admitted to COVID department at AVH, 54.2% were female and 33% of study participants were from Gaza governorate followed by Jerusalem 27%. Most participants 34.7% had first clinic visit after two days from the onset of COVID-19 symptoms. 45.8% were discharged to home while 13.9% died. All inflammatory markers that include ferritin, C-RP, IL-6 and D-dimer are in-creasing in all patients that were admitted to hospital; IL-6 and D-dimer were significant inflammatory markers in relation to the mortality rate. The study found the risk of mortality with IL-6 mean (218.5), and D-dimer mean (12). Furthermore there was a relation between increased risk of mortality and im-mune comprised. Conclusion: Mortality rate increased among COVID-19 pa-tients when IL-6 was higher than 218.5 and D-dimer higher than 12, and there was a relationship between increased risk of mortality and immune comprised.

Significance and Associated Factors of Long-Term Sequelae in Patients after Acute COVID-19 Infection in Korea.

BackgroundAs the coronavirus disease 2019 (COVID-19) pandemic has progressed, there has been a growing awareness of the long-term impacts of the COVID-19 infection. However, until recently, there was no published study that investigated COVID-19-related sequelae and related factors for greater than six months from the onset of COVID-19 symptoms or the time of COVID-19 diagnosis in Korea.Materials and MethodsOnline survey and statistical analysis were conducted by Kyungpook National University Hospital on 5,252 patients diagnosed as COVID-19 between February 18, 2020 and March 14, 2020. Responders aged between 16 and 70 years were included. Long-term sequelae were defined as persistent symptoms or signs ≥ 6 months after acute COVID-19 infection. The survey was conducted from September 8, 2020 to September 10, 2020. Clinical characteristics and self-reported clinical sequelae of the responders were analyzed to investigate the prevalence and factors associated with sequelae using descriptive and multivariate logistic regression analysis.ResultsThe median period from the date of the first symptom onset or COVID-19 diagnosis to the time of the survey was 195 (interquartile range [IQR] 191 - 200) days. The response rate was 17.1% (900 out of 5,252). The median age was 31 (IQR 24.0 - 47.0) years old, and 627 responders were female (69.7%). Regarding the disease severity, 29 (3.2%) were asymptomatic, 763 (84.8%) mild, 86 (9.6%) moderate, 17 (1.9%) severe, and 5 (0.6%) critical. In total, 591 (65.7%) responders suffered from COVID-19-related long-term sequelae and 78 (8.6%) responders were receiving outpatient treatment for COVID-19-related long-term sequelae. The most common symptoms identified during the isolation period were anosmia and ageusia at 44.5% and 43.5%, respectively. Fatigue was the most common long-term sequelae, accounting for 253 (26.2%) responders, followed by concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression, which accounted for over 20%. Female gender was identified as the factor associated with mental and psychological long-term sequelae (P <0.05).ConclusionThe results showed that the rate of COVID-19-related long-term sequelae was 65.7%. The most common long-term sequela was fatigue. The risk factor identified was female gender. It was found that the long-term sequelae had various manifestations, including mental and psychological aspects. To improve the care of COVID-19 recovered patients with COVID-19-related long-term sequelae, the participation of a comprehensive and an interdisciplinary group of researchers is required.

Optimizing COVID-19 surveillance in long-term care facilities: a modelling study

BackgroundLong-term care facilities (LTCFs) are vulnerable to outbreaks of coronavirus disease 2019 (COVID-19). Timely epidemiological surveillance is essential for outbreak response, but is complicated by a high proportion of silent (non-symptomatic) infections and limited testing resources.MethodsWe used a stochastic, individual-based model to simulate transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along detailed inter-individual contact networks describing patient-staff interactions in a real LTCF setting. We simulated distribution of nasopharyngeal swabs and reverse transcriptase polymerase chain reaction (RT-PCR) tests using clinical and demographic indications and evaluated the efficacy and resource-efficiency of a range of surveillance strategies, including group testing (sample pooling) and testing cascades, which couple (i) testing for multiple indications (symptoms, admission) with (ii) random daily testing.ResultsIn the baseline scenario, randomly introducing a silent SARS-CoV-2 infection into a 170-bed LTCF led to large outbreaks, with a cumulative 86 (95% uncertainty interval 6–224) infections after 3 weeks of unmitigated transmission. Efficacy of symptom-based screening was limited by lags to symptom onset and silent asymptomatic and pre-symptomatic transmission. Across scenarios, testing upon admission detected just 34–66% of patients infected upon LTCF entry, and also missed potential introductions from staff. Random daily testing was more effective when targeting patients than staff, but was overall an inefficient use of limited resources. At high testing capacity (> 10 tests/100 beds/day), cascades were most effective, with a 19–36% probability of detecting outbreaks prior to any nosocomial transmission, and 26–46% prior to first onset of COVID-19 symptoms. Conversely, at low capacity (< 2 tests/100 beds/day), group testing strategies detected outbreaks earliest. Pooling randomly selected patients in a daily group test was most likely to detect outbreaks prior to first symptom onset (16–27%), while pooling patients and staff expressing any COVID-like symptoms was the most efficient means to improve surveillance given resource limitations, compared to the reference requiring only 6–9 additional tests and 11–28 additional swabs to detect outbreaks 1–6 days earlier, prior to an additional 11–22 infections.ConclusionsCOVID-19 surveillance is challenged by delayed or absent clinical symptoms and imperfect diagnostic sensitivity of standard RT-PCR tests. In our analysis, group testing was the most effective and efficient COVID-19 surveillance strategy for resource-limited LTCFs. Testing cascades were even more effective given ample testing resources. Increasing testing capacity and updating surveillance protocols accordingly could facilitate earlier detection of emerging outbreaks, informing a need for urgent intervention in settings with ongoing nosocomial transmission.

Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19

Coronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production. To determine whether fluvoxamine, given during mild COVID-19 illness, prevents clinical deterioration and decreases the severity of disease. Double-blind, randomized, fully remote (contactless) clinical trial of fluvoxamine vs placebo. Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater. One hundred fifty-two participants were enrolled from the St Louis metropolitan area (Missouri and Illinois) from April 10, 2020, to August 5, 2020. The final date of follow-up was September 19, 2020. Participants were randomly assigned to receive 100 mg of fluvoxamine (n = 80) or placebo (n = 72) 3 times daily for 15 days. The primary outcome was clinical deterioration within 15 days of randomization defined by meeting both criteria of (1) shortness of breath or hospitalization for shortness of breath or pneumonia and (2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater. Of 152 patients who were randomized (mean [SD] age, 46 [13] years; 109 [72%] women), 115 (76%) completed the trial. Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events. In this preliminary study of adult outpatients with symptomatic COVID-19, patients treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. However, the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures. ClinicalTrials.gov Identifier: NCT04342663.

Predicting Venous Thromboembolic Events in Patients with Coronavirus Disease 2019 Requiring Hospitalization: an Observational Retrospective Study by the COVIDIC Initiative in a Swiss University Hospital.

Background Coronavirus disease 2019 (COVID-19) can result in profound changes in blood coagulation. The aim of the study was to determine the incidence and predictors of venous thromboembolic events (VTE) among patients with COVID-19 requiring hospital admission. Subjects and Methods. We performed a retrospective study at the Lausanne University Hospital with patients admitted because of COVID-19 from February 28 to April 30, 2020. Results Among 443 patients with COVID-19, VTE was diagnosed in 41 patients (9.3%; 27 pulmonary embolisms, 12 deep vein thrombosis, one pulmonary embolism and deep vein thrombosis, one portal vein thrombosis). VTE was diagnosed already upon admission in 14 (34.1%) patients and 27 (65.9%) during hospital stay (18 in ICU and nine in wards outside the ICU). Multivariate analysis revealed D-dimer value > 3,120 ng/ml (P < 0.001; OR 15.8, 95% CI 4.7-52.9) and duration of 8 days or more from COVID-19 symptoms onset to presentation (P 0.020; OR 4.8, 95% CI 1.3-18.3) to be independently associated with VTE upon admission. D-dimer value ≥ 3,000 ng/l combined with a Wells score for PE ≥ 2 was highly specific (sensitivity 57.1%, specificity 91.6%) in detecting VTE upon admission. Development of VTE during hospitalization was independently associated with D-dimer value > 5,611 ng/ml (P < 0.001; OR 6.3, 95% CI 2.4-16.2) and mechanical ventilation (P < 0.001; OR 5.9, 95% CI 2.3-15.1). Conclusions VTE seems to be a common COVID-19 complication upon admission and during hospitalization, especially in ICU. The combination of Wells ≥ 2 score and D − dimer ≥ 3,000 ng/l is a good predictor of VTE at admission.

High Probability of Long Diagnostic Delay in Coronavirus Disease 2019 Cases with Unknown Transmission Route in Japan.

Long diagnostic delays (LDDs) in patients with coronavirus disease 2019 (COVID-19) might decrease the effectiveness of patient isolation in reducing subsequent transmission. We assumed that direction of government considerably increased probability of LDD among COVID-19 cases with unknown exposure in Japan. This study aimed to investigate association of route of case detection and proportion of LDD of COVID-19 in Japan. We included confirmed COVID-19 patients with symptom onset between the ninth and eleventh week in 2020, in 6 prefectures of Japan. LDD was defined as the duration between COVID-19 symptom onset and confirmation ≥6 days. We used multivariable logistic regression analyses to elucidate factors associated with LDD. The mean diagnostic delay for 364 cases was 6.3 days. Proportion of LDD was 38% for cases with known exposure, and 65% for cases with unknown exposure. The probability of LDD in cases with unknown exposure was significantly higher than that for known exposure cases (adjusted odds ratio: 2.38, 95% confidence interval: 1.354–4.21). Early PCR test after symptom onset, strengthening of PCR test capacity, and investigations to study impact of high proportion of LDD in cases without known exposure might be necessary.

Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients\u2019 performance: a prospective observational cohort study

BackgroundSevere coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology.MethodsWe herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing.ResultsWe investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia.DiscussionAlterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19.Trial registrationClinicalTrials.gov number: NCT04416100.

Cerebral Venous Thrombosis in Patients with COVID-19 Infection: a Case Series and Systematic Review

BackgroundThere has been increasing reports associating the coronavirus disease 2019 (COVID-19) with thromboembolic phenomenon including ischemic strokes and venous thromboembolism. Cerebral venous thrombosis (CVT) is a rare neurovascular emergency that has been observed in some COVID-19 patients, yet much remains to be learnt of its underlying pathophysiology. ObjectiveWe present a case series of local patients with concomitant COVID-19 infection and CVT; and aim to perform a systematic review of known cases in the current literature. MethodsWe describe two patients with concomitant COVID-19 infection and CVT from a nationwide registry in Singapore. We then conducted a literature search in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 11th June 2020. All studies reporting CVT in COVID-19 patients were included. ResultsNine studies and 14 COVID-19 patients with CVT were studied. The median age was 43 years (IQR=36-58) and majority had no significant past medical conditions (60.0%). The time taken from onset of COVID-19 symptoms to CVT diagnosis was a median of 7 days (IQR=6-14). CVT was commonly seen in the transverse (75.0%) and sigmoid sinus (50.0%); 33.3% had involvement of the deep venous sinus system. A significant proportion of patients had raised D-dimer (75.0%) and CRP levels (50.0%). Two patients reported presence of antiphospholipid antibodies. Most patients received anticoagulation (91.7%) while overall mortality rate was 45.5%. ConclusionsThe high mortality rate of CVT in COVID-19 infection warrants a high index of suspicion from physicians, and early treatment with anticoagulation should be initiated.

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes. We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders. Of 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17-1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, p < 0.001). Neurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

COVID-19: What do we know?

• Evidence regarding the provision of orthodontic care during the COVID-19 pandemic is examined.

Letter: Thrombotic Neurovascular Disease in COVID-19 Patients.

Letter: Thrombotic Neurovascular Disease in COVID-19 Patients.

Cutaneous Manifestations of COVID-19: An Evidence-Based Review

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has affected 18 million people and killed over 690,000 patients. Although this virus primarily causes respiratory symptoms, an increasing number of cutaneous manifestations associated with this disease have been reported.ObjectiveThe aim of this review was to collate and categorize the dermatologic findings reported in patients with COVID-19 and identify specific lesions that may facilitate diagnosis and prognostication.MethodsAn evidence-based review of the PubMed database was conducted on 14 May, 2020 using the search terms “Covid-19 skin,” “Covid-19 rash,” “Covid-19 exanthem,” and “Covid-19 chilblains.” Peer-reviewed publications containing original COVID-19 patient cases and a discussion of the associated cutaneous findings were included in the analysis.ResultsThe literature search identified 115 records, of which 34 publications describing 996 patients with dermatologic conditions were included. Case reports (n = 15), case series (n = 13), and observational prospective studies (n = 4) were the most common publication types. Acral lesions resembling pseudo-chilblains were the most frequent lesion identified (40.4% of cases), appearing in young adults (mean age, 23.2 years) after the onset of extracutaneous COVID-19 symptoms (55/100 patients). Erythematous maculopapular rashes affected 21.3% of patients, most frequently impacting middle-aged adults (mean age, 53.2 years) and occurring at the same time as non-cutaneous symptoms (110/187 patients). Vesicular rashes affected 13.0% of patients, appearing in middle-aged adults (mean age, 48.3 years) after the onset of other symptoms (52/84 patients). Urticarial rashes affected 10.9% of patients, appearing in adults (mean age, 38.3 years) and occurring at the same time as non-cutaneous symptoms (46/78 patients). Vascular rashes resembling livedo or purpura were uncommon (4% of cases), appearing in elderly patients (mean age, 77.5 years) and occurring at the same time as non-cutaneous COVID-19 symptoms (18/29 patients). Erythema multiforme-like eruptions, although infrequent (3.7% of cases), affected mostly children (mean age, 12.2 years).ConclusionsVesicular rashes may suggest an initial diagnosis of COVID-19, acral lesions may be most appropriate for epidemiological uses, and vascular rashes may be a useful prognostic marker for severe disease. As a potential correlate to disease severity, prognosis, or infectibility, it is critical that all healthcare professionals be well versed in these increasingly common cutaneous manifestations of COVID-19.

Editors' note: COVID-19 presenting with ophthalmoparesis from cranial nerve palsy.

Dr. Dinkin et al. reported 2 cases with MRI confirmation of cranial nerve inflammation within several days of systemic symptoms of the novel coronavirus disease 2019 (COVID-19). Both patients tested positive for SARS-CoV-2 by PCR from a nasal swab, and both were treated with hydroxychloroquine (one also with intravenous immunoglobulin), with mild short-term improvement. The authors suggest the inflammatory cranial neuropathies could have been because of a postviral immune-related response. Dr. Machado wonders whether the cranial neuropathies could have resulted from direct viral invasion, given their onset shortly after the viral symptoms started. As noted by Gutiérrez-Ortiz et al. (Dinkin et al., reference 2 below) 2 patients developed evidence of cranial nerve inflammation and autoimmune neuropathy within 3–5 days of COVID-19 symptom onset. Each of these 4 cases highlight the accelerated time course of inflammatory cranial neuropathies after systemic manifestations of COVID-19, which seems to be more rapid than has been typically reported for variants of Guillain-Barré syndrome after other infectious illnesses. These observations may also support that there is an asymptomatic phase of this viral infection during which an immune response may be generated. Dr. Dinkin et al. reported 2 cases with MRI confirmation of cranial nerve inflammation within several days of systemic symptoms of the novel coronavirus disease 2019 (COVID-19). Both patients tested positive for SARS-CoV-2 by PCR from a nasal swab, and both were treated with hydroxychloroquine (one also with intravenous immunoglobulin), with mild short-term improvement. The authors suggest the inflammatory cranial neuropathies could have been because of a postviral immune-related response. Dr. Machado wonders whether the cranial neuropathies could have resulted from direct viral invasion, given their onset shortly after the viral symptoms started. As noted by Gutiérrez-Ortiz et al. (Dinkin et al., reference 2 below) 2 patients developed evidence of cranial nerve inflammation and autoimmune neuropathy within 3–5 days of COVID-19 symptom onset. Each of these 4 cases highlight the accelerated time course of inflammatory cranial neuropathies after systemic manifestations of COVID-19, which seems to be more rapid than has been typically reported for variants of Guillain-Barré syndrome after other infectious illnesses. These observations may also support that there is an asymptomatic phase of this viral infection during which an immune response may be generated.

COVID-19 After Effects: Concerns for Singers

COVID-19 After Effects: Concerns for Singers

COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature.

Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean d-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated d-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.Electronic supplementary materialThe online version of this article (10.1007/s11239-020-02228-y) contains supplementary material, which is available to authorized users.

Detecting SARS-CoV-2 RNA in conjunctival secretions: Is it a valuable diagnostic method of COVID-19?

The main purpose of this study is to evaluate the presence of viral RNA of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) in conjunctival swab specimen of coronavirus disease 2019 (COVID‐19) patients with and without conjunctivitis to establish the diagnostic value of reverse transcription‐polymerase chain reaction (RT‐PCR) in each case and to describe its clinical characteristics. A cross‐sectional study was conducted at the Hospital Clinico San Carlos of Madrid, Spain. Thirty‐six subjects from the COVID admission unit with laboratory‐confirmed SARS‐CoV‐2 infection were included. Conjunctival swabs were collected from 18 patients with conjunctivitis and 18 patients without conjunctivitis and RT‐PCR was performed. Conjunctival swab was collected from both eyes of 36 patients (72 eyes), detecting SARS‐CoV‐2 RNA in conjunctival swab of two patients (5.5%). Among the 18 patients with conjunctivitis, only one of them (5.5%) showed positive results. Likewise, SARS‐CoV‐2 RNA was detected in one patient without conjunctivitis (5.5%). The mean age of the 36 patients was 67.9 years (range, 28‐92 years) and the male‐to‐female ratio was 0.44 (16:20). The mean days since the onset of COVID‐19 symptoms until conjunctivitis manifestation was 8 (range, 1‐24 days). The mean duration of the conjunctivitis was 3 days (range, 1‐7 days). SARS‐CoV‐2 RNA may be detected in conjunctival swabs of both patients with and without conjunctivitis. This study revealed the same rate of positive results amongst the group with and without conjunctivitis, suggesting that detecting SARS‐CoV‐2 in ocular fluids is not conditioned on the presence of conjunctivitis. The presence of SARS‐CoV‐2 RNA in ocular samples highlights the role of the eye as a possible route of transmission of the disease.