Diagnostic

Since the start of the pandemic, COVID-19-related anosmia became a prominent marker for infection; however, the time course and reversibility remain unclear. This study follows the clinical course and prognosis of a sample of patients with COVID-19 anosmia, evaluated at 4 month intervals for 1 year.

Methods

• Sample: 97 patients with PCR positive COVID-19 and acute smell loss (>7 days)

• 51patients underwent both subjective and objective olfactory test, 46 underwent only a subjective assessment

Results

• • For patients who underwent both subjective and objective testing: After subjective assessment at 4 months, 23 of 51 patients (45.1%) reported full recovery of olfaction, 27 of 51 patients (52.9%) reported partial recovery, and 1 of 51 patients (2.0%) reported no recovery. However, on objective testing, 43 of 51 patients (84.3%) were normosmic. At 8 months, objective olfactory assessment confirmed full recovery in 49 of 51 patients (96.1%).

  • For patients who underwent the subjective assessment alone: 13 of 46 patients (28.2%) reported satisfactory recovery at 4 months, and the remaining 33 patients (71.7%) did so by 12 months.

Conclusion

• • Near complete recovery rate in COVID-19 related anosmia after 12 months

  • Supports previous animal research claiming COVID-19–related anosmia is likely due to peripheral inflammation

  • Data confirms discrepancies between subjective and objective measurements in olfaction

This article investigates a proinflammatory syndrome with characteristics similar to Kawasaki disease (KD) and toxic shock syndrome (TSS) in pediatric patients with severe COVID-19 infection.

Methods

• Inclusion Criteria (n = 17)

  • Patient under 21 years of age

  • Received care at Columbia University Irving Medical Center/NewYork-Presbyterian Morgan Stanley Children’s Hospital in New York City between April 18 and May 5, 2020

  • Presented with prolonged fever, systemic inflammation, shock, end-organ dysfunction, or symptoms similar to KD or TSS

  • Recent severe SARS-CoV-2 infection

• Laboratory tests and assessments of cardiac function were performed on admission

• SARS-CoV-2 infection confirmed via RT-PCR or serology

Results

Physical Exam Findings - n (%)

• • Gastrointestinal symptoms (abdominal pain, vomiting, diarrhea) - 15 (88%)

  • Mucocutaneous findings

    • Rash - 12 (71%)

    • Conjunctivitis - 11 (65%)

    • Lip redness/swelling - 9 (53%)

  • Shock at presentation - 13 (76%)

  • Hypoxic at presentation - 3 (18%)

  • Met criteria for KD - 8 (47%)

  • Met criteria for incomplete KD - 5 (29%)

Inflammatory Markers - n (%)

• • White Blood Cell

    • Lymphopenia - 12 (71%)

    • Bandemia - 11 (65%)

  • Elevated troponin T - 14 (82%)

  • Elevated NT-proBNP - 15 (86%)

  • Elevated IL-6 - 16 (94%)

  • Elevated IL-2R, IL-18, CXCL9 - 8 (47%)

Cardiac function - n (%)

• • Left ventricular function

    • Normal - 6 (35%)

    • Mild decrease - 5 (29%)

    • Mild-moderate decrease - 4 (24%)

    • Moderate-severe decrease - 2 (12%)

  • Pericardial effusion - 8 (47%)

Discussion

Abnormal cardiac signs found in this study may indicate the need for long-term surveillance of this patient population

Limitations include:

• • Small study size

  • Short follow-up period

  • Inability to establish causality

The alarming rate of increase in the number of confirmed cases of COVID-19 forced the field of ophthalmology into a standstill. The American Academy of Ophthalmology (AAO) drastically changed the practice of ophthalmology to providing only urgent and emergent care while putting a pause to other non-emergent cases; acknowledging the “existential crisis” that is COVID pandemic. This measure was endorsed and instituted without any clear end as to when normal practices will resume.

The AAO recommendation led to significant reduction in office visits, a shift to telemedicine and provision of solely urgent and emergent care by different practices which resulted in furloughs and laying off of staff and ophthalmologists.

The problem at hand is: how do we return to a normal practice of ophthalmology? According to the author, a good portion of the practice is expected to change and some things will undoubtedly remain unchanged. Both patients and physicians will have a transformed expectation for clinical encounters; some practices will emerge intact while others will be left in pits with no fragments to piece together due to lack of staffing, resources and unattainable patient and staff expectations. Until herd immunity is achieved, access to reliable and affordable testing is another problem to grapple with. So is “changes in medical education at all levels involving public health, disaster management and cross-specialty education.”

Other expected changes would include changes in insurance markets to reflect the evolving new normal accounting for telemedicine and other appropriate services; decrease corporatization of ophthalmology practices by private equity (PE) companies or struggle for acquisition of "capital and management expertise”. Further, some non-physician clinicians temporarily allowed to perform procedures without physician supervision are now advocating for such change to become permanent. Telemedical services could be one way to effectively manage the backlog of healthcare delivery and evolving patients demands post pandemic.

For the foreseeable future, coronaviruses related research will be prioritized, and changes may be made to FDA regulations to allow for expedited clinical trials and approval pathways.

A successful transition back to patient care will be determined by how effective we identify and address the above-mentioned changes, and reconciling them with “societal expectations” for swiftly transforming delivery of healthcare.

Introduction: Few reports have associated SARS-CoV2 with ocular abnormalities. There is suspicion that SARS-CoV2 could be transmitted through the eye. However, no medical literature has reported a direct relationship between SARS-CoV2 and ocular abnormalities. The goal of the study “was to evaluate ocular involvement systematically in patients highly suspected of having or confirmed to have COVID-19.”

Methods: 38 consecutive patients who were hospitalized for COVID-19 were recruited from Feb. 9 to Feb. 15, 2020. Patients symptoms, ocular manifestation, chest CT scans, blood test results and RT-PCR from conjunctival and nasopharyngeal were gathered and analyzed.

Results:

● 65.8% (25) of the patients were male, the mean age was 65.8 years.

● 28 (73.7%) patients tested positive for COVID-19 via RT-PCR from nasopharyngeal swabs, and 2 out of 28 (5.2%) patients tested positive for COVID-19 via both conjunctival and nasopharyngeal swabs. 10 of 38 patients were deemed to have COVID-19 based on guidelines for diagnosis.

● 12 of 38 patients developed signs of conjunctivitis including conjunctival hyperemia, epiphora, and increased secretion. 4 of 12 patients were categorized as moderate cases of COVID-19, 2 of 12 as severe, and 6 of 12 as critical with respiratory failure or shock or multiorgan dysfunction. 1 of 6 critical patients had epiphora as the initial symptoms of COVID-19. Notably, there was no blurry vision.

● Patients with ocular abnormalities were found to have higher WBCs and neutrophils, higher levels of procalcitonin, CRP and LDH than those with no ocular findings.

● 11 of 12 with ocular findings tested positive via RT-PCR from nasopharyngeal swabs and 2 of 11 tested positive on both conjunctival and nasopharyngeal RT-PCR.

Discussion and Conclusions: It was found that one-third (31.6%) of total patients had ocular findings with majority among COVID-19 patients with severe systemic involvement and abnormal blood test results. There is low prevalence (5.2%) of COVID-19 nucleotides in the conjunctival specimen obtained from infected patients. Only 1 patient had conjunctivitis as the first, presenting symptom of COVID-19. It is possible that SARS-CoV-2 could be transmitted via the eye.

· Background: The main presenting symptoms of SARS-COV2 infection include fever, cough, and dyspnea. However apart from these respiratory symptoms, gastrointestinal (GI) manifestations are also common at the initial presentation. GI symptoms were previously seen with both SARS and MERS infections as well. Data from patients with SARS estimated that 16-73% of patients had diarrhea during their illness, and fecal shedding was found in 86-100% of the patients during day 6-14 and could persist for >30 days. Due to this, GI manifestations of COVID-19 poses a diagnostic challenge for patients presenting with mild symptoms. It also signifies potential fecal transmission of this virus. As the number of cases continues to increase rapidly, this study proposes that it is crucial to summarize the GI manifestations of COVID-19 and the temporal patterns of fecal viral shedding.

· Study Methodology: This study includes data from a cohort of patients (n=59) with COVID-19 in Hong Kong and a systematic review of a meta-analysis of published studies (n=4243) through March 11th, 2020. The data collected included the prevalence of GI symptoms (anorexia, nausea, vomiting, abdominal pain, and diarrhea) and was analyzed using a random-effects model.

· Results: Of the cohort of 59 patients in Hong Kong, 15 patients (25.4%) had GI symptoms, and 9 patients (15.3%) had a stool that tested positive for the viral RNA. Fecal viral RNA was detected in 38.5% of patients with diarrhea and 8.7% of those without diarrhea. In the meta-analysis of the 4232 patients, the pooled prevalence of GI symptoms was 17.6%. Of these patients, 17.1% of patients with severe cases had GI symptoms, and 11.8% of those with non-severe cases had GI symptoms. The pooled prevalence of stool samples that were positive for viral RNA was 48.1%. Of these specific samples, 70.3% were collected after respiratory samples were negative for the virus.

· Discussion: Joint analysis from a Hong Kong cohort and a meta-analysis of publications, showed that the prevalence of GI symptoms in COVID-19 patients is 17.6%. Viral RNA was found in the stool samples of these patients, even after respiratory samples tested negative. This data indicates that healthcare workers should proceed with caution when collecting fecal samples or performing endoscopic procedures in patients with COVID-19. Furthermore, this is important for diagnostic purposes and for everyone to be aware during patient recovery.

Study Background: Based on early data regarding COVID-19 patients in Wuhan, China, it was found that the proportion of deaths of patients over 60 years old made up 81% of the total deaths in the country. Data showed that the case-fatality rate (CRF) is much higher in patients over 60 years old and increased by age. Patients over 80 years had a CRF of 14.8%, while patients from 60-69 had a CRF of 3.6%. This study investigates the clinical characteristics and prognostic factors of patients over the age of 60 in China. It aims to provide clinical evidence that can hopefully lead to early risk stratification and improve clinical practice while reducing the death rate in this population.

Study Methodology: This is a retrospective, single-center study that included (n=339) patients over 60 years old with confirmed cases of COVID-19. These were patients admitted from January 1st to February 6th to an isolation ward of Renmin Hospital of Wuhan University. Patients were divided into four categories after admission which include mild (confirmed without pneumonia), moderate (confirmed with pneumonia), severe (dyspnea, RR>30, O2 sat <93% or lung infiltrates >50% within 24-8 hours) and critical (respiratory failure, shock or end-organ failure). The primary outcomes were survival until March 5th or death. The data collected included demographics, clinical features, comorbidities, laboratory tests, imaging, and complications.

Results: Of the 339 patients included, the mean age was 71 years old, and 51% were female. Of the patients, 23.6% were critical, 46.9% were severe, and 29.5% were moderate. 60.7% had at least one comorbidity, while 23.9% has two or more. Common comorbidities included hypertension, diabetes, and cardiovascular disease. At the study conclusion on March 5th, 2020, 26% of patients were discharged, 54% remained hospitalized, and 19.2% percent died. The median duration for the hospital was 21 days. The participants who died were majority male, significantly older, shorter stay (5 days), and had comorbidities of hypertension, cardiovascular disease, and COPD. Common complications included bacterial infection, liver enzyme abnormalities, and ARDS.

Discussion: SAR-COV-2 infection caused increased severity and fatality in this sample population of elderly patients. Constant monitoring and timely treatment are essential in this population. A high proportion (70%) of the patients were considered severe or critical cases, and a high fatality rate of 19% was observed in the study population. The median survival time from admission was five days, which indicates a rapid disease progression in this age group. The comorbidities that are predictive of poor survival are cardiovascular disease and COPD. During admission, dyspnea, lymphocytopenia, and ARDS were also predictive of worse outcomes. Interestingly, increased lymphocyte count was predictive of better results.

Chest CT is widely used in the diagnosis and progression of COVID-19, but it exposes the body to harmful radiation. This is mitigated by the potential impact of radiologic findings in the patient’s treatment plan. However, the risk can become too significant if a patient is subjected to subsequent CT scans as the disease progresses. Additionally, CT is often used for initial detection of COVID-19, resulting in significant cumulative radiation exposure among the population. This study establishes an ultra-low-dose CT protocol with 86.7% sensitivity, 91.1% PPV, and 90.3% NPV in the diagnosis of COVID-19, using RT-PCR as gold standard. These impressive values improved even further in patients who experienced symptoms for more than 48 hours. They predict the reduced radiation exposure can be particularly useful in patients younger than 40 years old. Additionally, median wait time for radiologic reports was only 25 minutes; much shorter than the suggested 1 hour 55min waiting for RT-PCR results. The authors identified a few potential pitfalls of the study. First, it is imperative to recognize that we are in a public health crisis, so imaging strategies should not be selected solely based on radiation dose. Also, as testing kits become more rapid and more accurate, chest CT could become less useful in the diagnosis of COVID-19. However, I believe it will continue to be useful for evaluating disease progression.

Currently, a virus-specific real-time polymerase chain reaction (RT-PCR) test is used to diagnose patients with COVID-19. These tests are limited by their scarcity and can take up to 2 days to complete. While CT can aid in diagnosis of COVID-19, some patients who are early in the disease course may have normal scans. Researchers at Mt Sinai implemented an algorithm powered by artificial intelligence (AI) as an alternative method to reach a COVID-19 diagnosis. They trained the neural network using patient scans and COVID-19 status determined by RT-PCR. The input for the algorithm includes segmented lungs from a chest CT, clinical symptoms, possible exposures, and lab tests. Among 279 patients who tested positive for COVID-19 with RT-PCR, the algorithm obtained equal sensitivity when compared to a “senior thoracic radiologist.” More impressively, the algorithm correctly identified 17 of 25 patients (68%) who were COVID-19 positive but had normal radiologic findings. On the other hand, the radiologist, using the same patients and dataset (scans, symptoms, exposures, and labs), incorrectly labeled all 25 patients as COVID-19 negative. This is credited to the multifactorial input of the algorithm. The algorithm has been proposed as a possible rapid screening tool to aid in triage. The system could flag suspected infected patients for more immediate review by a radiologist. The researchers predict this could be especially useful in areas with a significant burden of COVID-19.

During this unprecedented time of uncertainty amidst the coronavirus pandemic, several specialties have noted a decrease in non-COVID patients presenting with acute complaints. This may suggest that Americans are adhering to social distancing recommendations, and are avoiding healthcare facilities due to psychological, social, and health system facilitated factors. The authors of this study conducted in New Jersey, a state that has been heavily affected by the pandemic, postulate that there has been a decrease in patients presenting with mild ischemic stroke symptoms between March 1st and April 15th compared to pre-COVID-19 conditions due to these psychosocial factors and the restrictions that have been implemented. They hypothesize that while the overall number of acute ischemic strokes has fallen during this time period, the severity of these ischemic strokes will be higher compared to the pre-COVID-19 period.

This study was a retrospective analysis of a prospective observational cohort of 328 participants, age ≥18, with a diagnosis of acute ischemic stroke given between October 1st, 2019, and April 15th, 2020 at the Cooper University Hospital, New Jersey. All patients underwent a non-contrast head CT to rule out hemorrhage or other structural brain lesions as the cause of their neurological symptoms. The data collected included daily number of new acute stroke diagnoses, stroke etiology classification, stroke severity score(NIHSS), whether an MRI was preformed, presence of a proximal LVO (Large Vessel Occlusion): (ICA, M1, M2, basilar), timing and use of thrombolytic and endovascular treatment, time from evaluation to imaging and treatment, length of hospital stay, discharge disposition, and demographic data.

The results showed that there was a significant decline in the daily number of new acute stroke diagnoses at the tertiary care center during the six weeks of the COVID-19 pandemic when compared to the pre-COVID-19 period. There was no significant difference in the age, gender, race, risk factors or stroke severity during the COVID period compared to the pre-COVID period. This refutes the authors’ postulation that during the COVID period the acute ischemic strokes would have higher severity scores. The authors discuss that the NIHSS is not a perfect tool for assessing severity, and that when considering a variety of other factors, such as in hospital mortality and a higher percentage of LVO, stroke severity was likely higher during the COVID period than preceding it. The authors noted a significantly smaller number of patients presented by car or by EMS, suggesting that patients seem more hesitant to call 911. The authors also suggest that with social isolation, less patients are coming in by themselves for evaluation possibly due to these social distancing restrictions. With social distancing, patients may not come in contact with family as often, and it is often family members who notice mild neurological symptoms in ischemic stroke patients that they themselves haven’t noticed. Furthermore, some patients may be declining to seek medical attention because of recent unemployment and health insurance concerns. Also of note, the authors report that there was no delay in care from the last known well time to arrival at the medical center or from arrival to treatment. This suggests that the stroke response team was able to adequately manage these patients during the COVID period and with a slight improvement in time to thrombolytic treatment in those patients where thrombolysis was required. There was a decreased use of MRI for assessing acute ischemic stroke, however, the authors maintain that this did not significantly affect the reported number of daily ischemic stroke diagnoses.

Throughout the study it was unclear to me whether the study included COVID+ lab confirmed patients. The study noted that only 9 patients had available polymerase chain reaction test results for the SARS-CoV-2 virus during the COVID-19 period, and only 1 tested positive. Because COVID-19 has been shown to result in significant inflammation and increased stroke risk, I was surprised that this connection was not addressed, and that the methods section did not specify whether the study would include or exclude COVID-19+ patients. The study was not adequate to determine whether the milder cases of acute stroke were diagnosed less frequently during the COVID period. However, the authors made a strong argument to suggest that though the data does not support their anecdotal observations, that it is likely that participants with milder acute stokes did not seek care as often during the COVID period compared to the period prior.

Study Background

Emergency department physicians are charged with the responsibility of identifying and isolating suspected cases of COVID-19 to prevent nosocomial transmission. This is a difficult task, given that patients with COVID-19 may be asymptomatic, present with atypical symptoms, or present with symptoms indistinguishable from common respiratory viruses. Accurate case definitions, therefore, become a critical triaging tool.

Study Methodology/Results

This study was conducted at Singapore General Hospital, a tertiary care center with 1,785 beds. Researchers tested all ED admissions with respiratory symptoms over a 3-month period, constituting a total of 1,841 cases. Seventy cases of COVID-19 were confirmed. From this data, researchers determined the sensitivity and specificity of screening criteria, allowing for a risk-stratified approach for PPE usage by expanding a preexisting ED “fever area.” The cumulative sensitivity of broadened internal screening criteria was higher than the published official case criteria. There were no reported cases of nosocomial transmission from intra-ED exposure.

Discussion

This article highlights the capability of internal screening criteria to more accurately triage suspected cases of COVID-19. This is particularly beneficial for facilities with limited PPE, as to facilitate the most effective usage of these resources. However, if screening criteria are broad, as was the case at Singapore General Hospital, then emergency departments must be prepared to house a larger number of suspected cases. Ultimately, these data compel an argument that individual physicians and hospital systems should have more autonomy in triaging clinical suspicion of COVID-19. This study was limited by the sensitivity and specificity of PCR testing for SARS-CoV-2, which are currently unknown.

Study Background

Awake proning has been shown to decrease intubation and improve outcomes in hypoxic ARDS patients and has thus become the standard treatment. Many with COVID-19 present with hypoxia, tachypnea, and chest radiograph findings similar to ARDS. These concerning findings have resulted in early intubation and rapid depletion of ventilator stockpiles. This study examined the effect of proning on awake, non-intubated patients with suspected or confirmed COVID-19 in the emergency department, and its impact on oxygenation.The study was conducted at an urban, academic ED in New York City over the course of one month. Fifty adult patients with confirmed or suspected COVID-19 with hypoxia without resolution despite supplemental oxygen. The change in SpO₂ was measured after 5 minutes of proning without a change in inspired oxygen. Comparison of the pre‐ to post‐median SpO₂ by the Wilcoxon Rank–sum test yielded P = 0.001. Of the fifty patients, thirteen required endotracheal intubation within 24 hours of arrival to the ED.

Discussion

This study demonstrated that hypoxic patients with COVID-19 had improved oxygen saturation as the result of awake, early proning, similar to that of patients with ARDS. This finding is of value to concerns surrounding the aerosolization of the virus during noninvasive ventilation and high flow nasal cannula and may prevent early intubation. Given that self-proning can be performed without assistance and without cost, early and frequent use is recommended, although the effect on disease severity and mortality is unkown. This study was limited by all other aspects of care being uncontrolled, so causality may not be concluded.

Introduction

Laboratory measures such as white blood cells, neutrophils, lymphocytes counts, D-dimer, albumin, and procalcitonin in patient blood samples may be predictive of their probability of developing severe COVID-19 infection.

Methods

• This study is a retrospective analysis of clinical data from 443 COVID-19 patients cared for in Wuhan Forth Hospital from January 16 – February 28, 2020

• Cases were categorized as:

  • Light: no pneumonia on imaging

  • Ordinary: pneumonia on imaging with fever and respiratory tract symptoms

  • Intensive: shortness of breath, respiratory rate greater than 30 breaths/min, oxygen saturation less than 93%

  • Critical: respiratory failure, shock, organ failure

• Light and ordinary cases were defined as non-severe; intensive and critical cases were defined as severe.

Results

• Parameters that were significantly higher in the severe group:

  • Cell counts: leukocytes, neutrophils, neutrophil-lymphocyte ratio (NLR)

  • Labs: D-dimer, C-reactive protein (CRP), procalcitonin, LDH, creatinine

• Parameters that were significantly lower in the severe group

  • Cell counts: lymphocytes, platelets

  • Labs: albumin

• Logistic regression indicated:

  • NLR (OR = 1.222) and CRP (OR = 1.017) were independent risk factors for severe infection.

  • Platelet count (OR = 0.995) was an independent protective factor for severe infection.

Discussion

• NLR and CPR could be useful measures for predicting the severity of COVID-19 cases

• A higher platelet count was associated with less severe disease

  • Further study is needed to determine if the low platelet counts associated with severe disease were due to thrombocytopenia.

Limitations

• Single-center retrospective study may limit the generalizability of results.

• Small sample size

• Some patients included in the study are still hospitalized, making it difficult to fully assess risk factors for poor outcomes.

Background of COVID-19

Coronavirus disease 2019 (COVID-19) emerged in Wuhan, China in December 2019 and spread globally. The Chinese government began screening for SARS-CoV-2 infection among individuals in close contact with confirmed COVID-19 patients. During the screening process, there were patients who tested positive for SARS-CoV-2 but did not display symptoms or signs throughout the disease course. The purpose of this study is to describe the clinical characteristics of asymptomatic and symptomatic patients from 26 transmission cluster series in Wuhan, China.

Methods

All consecutive patients with RT-PCR confirmed COVID-19 cases admitted to Zhongnan Hospital of Wuhan University from December 24, 2019 to February 24, 2020 were enrolled. Epidemiological, symptoms, signs, laboratory values, CT scans, treatment measures, and outcomes data were collected during the hospital stay. Nasopharyngeal swab samples were collected from patients with suspected SARS-Co-V2 infection. Patients were recruited from 26 cluster cases with confirmed history of exposure to the Hunan seafood market or close contact with a known infected person.

Results

Data was collected from 78 patients who met criteria with nasopharyngeal RT-PCR confirmed SARS-CoV-2 infection. The patients were hospitalized in the same medical area and provided the same treatments administered by the same health workers. 33 patients (42.3%) were asymptomatic and 45 patients (57.7%) were symptomatic. Symptoms were monitored daily, nasopharyngeal swabs were performed every 24 to 48 hours, repeat chest CTs were conducted 4 to 6 days and 6 to 7 days after initial imaging, and CD4+T lymphocyte counts were tested every 5 to 6 days. Asymptomatic patients were younger, had a higher proportion of women, had a lower proportion of liver injury, less consumption of CD4+T lymphocytes, faster lung recovery in CT scans, and shorter duration of viral shedding.

Discussion

Less consumption of CD4+T lymphocytes in asymptomatic infections suggests that immune system damage is milder than that of symptomatic cases. Asymptomatic patients may be unaware of the infection and consequently less likely to isolate, resulting in high rates of transmission. Despite a shorter duration of viral shedding and lower risk of a recurring positive test result, asymptomatic cases must be identified as early as possible to control transmission. The current study was limited by subjective observations of clinical differences between asymptomatic and symptomatic patients and further study is necessary.

During the COVID-19 pandemic there have been reports of fewer patients presenting to the emergency department with acute myocardial infarction. The current study examined this claim using data from Kaiser Permanente and included data from 21 medical centers and 255 clinics.

Methods

• Authors compared patient characteristics and weekly incidence rates of hospitalization (hospitalizations per 100,000 person weeks) for acute STEMI and NSTEMI before (January 1 to March 3, 2020) and after (March 4 to April 14, 2020) the first reported COVID-19 related death (March 4, 2020) and examined data from the same period in 2019

Results

• Weekly rate of hospitalization for acute MI decreased by 48% after the first COVID-19 death on March 4, 2020

  • Incidence rate ratio 0.52 (95% CI 0.40-0.68)

  • 4.1 patients per 100,000 person-weeks were hospitalized for acute MI prior to the first COVID-19 death (January 1 to March 3, 2020)

  • 2.1 patients per 100,000 person-weeks were hospitalized after the first COVID-19 related death (April 8 to April 14, 2020)

• Incidence rate ratio for NSTEMI and STEMI were similar

  • NSTEMI: 0.51 (95% CI 0.38-0.68)

  • STEMI: 0.60 (95% CI 0.33-1.08)

  • Comparison between post COVID-19 acute MI hospitalization rate (March 4 to April 14, 2020) and the same period in 2019 yielded similar results

• Among patients presenting with acute MI after the first COVID-19 death, the prevalence of preexisting coronary artery disease, previous MI and history of percutaneous coronary intervention were lower than during any pre-COVID-19 era

  • The prevalence of all historical data-points was decreased during the COVID-19 period, however, no explanation for this was offered

Introduction

This case series describes a set of five COVID-19 infected patients who were admitted to the ICU at Emory University who developed acute cor pulmonale. These five patients were present in the ICU between March 23rd and April 4th. All five developed acute right ventricular failure diagnosed on transthoracic echocardiogram, and four of the five progressed to cardiac arrest with only one of these surviving.

Key Points

• The most likely cause of the acute cor pulmonale in these patients was a pulmonary thromboembolism, although it was not confirmed in all cases.

• Providers should be aware of obstructive shock as a possible cause for hemodynamic instability in critically ill COVID-19 patients.

• This case series demonstrated the importance of further research for the use of thrombolytics and anticoagulation in severely ill COVID-19 patients.

Objective

This study aims to investigate the utility of hyposmia and hypogeusia as potential distinctive features to help guide medical professionals to investigate COVID-19 in patients presenting with influenza-like illness.

Background

• Early and accurate diagnosis of COVID-19 is essential in managing the illness.

• Patients may present with influenza-like illness (ILI) that may complicate diagnosis of COVID-19 vs. other respiratory infections.

• Symptoms that help distinguish COVID-19 from other respiratory infections, such as influenza, may help improve early and accurate COVID-19 diagnosis.

• Hyposmia and hypogeusia may be symptoms of COVID-19 infection.

Methods

• Study completed March 15-18, 2020 on patients who had undergone COVID-19 testing by RT-PCR of nasopharyngeal swab since February 16 at 3 infectious disease referral centers in western France (Rennes, Angers, and Nantes)

• Participants were invited by email or phone to complete a web-based survey asking the following questions: Have you been diagnosed with COVID-19 following diagnostic screening? Did you notice a loss of smell during your disease? Did you notice a loss of taste? Do you regularly suffer from ear, nose, and throat (ENT) disorders?

• Study approved by the Rennes University Hospital institutional review board; informed consent was waived.

Results

• 57% of contacted patients replied, 26% of whom reported a positive test for SARS-CoV-2

• Hyposmia reported by 20% of patients

• Hypogeusia reported by 24% of patients

• Both hyposmia and hypogeusia reported by 17% of patients

• ENT disorders reported by 32% of patients

• Strong association of hyposmia and hypogeusia with COVID-19 diagnosis, in patients both with and without ENT disorders.

• Best performance in patients with both hyposmia and hypogeusia without ENT disorder, with sensitivity of 42% (95% CI 27-58) and specificity of 95% (95% CI 90-98) for COVID-19 diagnosis

Discussion

• Hyposmia and hypogeusia together in patients with influenza-like illness and without ENT disorders has 42% sensitivity and 95% specificity for detecting SARS-CoV-2 infection

• Previous prevalence of smell and taste disorders in patients with COVID-19 was estimated at 5%, but data was obtained retrospectively from medical files which may have led to underestimation of the real prevalence

• Hyposmia and hypogeusia in patients with ILI may be a useful tool in diagnostic workup for suspected COVID-19

• These symptoms are easy to collect and may be useful in mass screenings or telemedicine settings

• Larger prospective studies are required to confirm these findings

Limitations

• Data were retrospectively collected through web-based survey and no other data on age, sex, or other symptoms were obtained.

• Data were collected anonymously so accuracy of responses could not be verified

• Small sample size and suboptimal response rate of 57%

• The SARS-CoV-2 RT-PCR tests used to confirm COVID-19 diagnosis had sensitivity of 60% which could have led to misclassification and diagnostic bias

Background

The first case of coronavirus disease 2019 (COVID-19) in the United States was reported on January 20, 2020 in Snohomish County, Washington. The University of Washington (UW) Virology Division has tested more than 73,000 patients since March 1, 2020. This article analyzes trends in positivity rates for SARS-CoV-2.

Methods

Nasopharyngeal swabs were collected from 17,232 patients in outpatient settings and 1,932 patients in 3 Seattle emergency departments. The samples were analyzed by a laboratory-developed reverse transcriptase-polymerase chain reaction test. Positivity rate was determined by fitting penalized cubic regression splines to binomial testing data, accounting for variation, and utilizing only the first positive test in patients with multiple tests. Statistical analysis was performed using a two-sided chi-squared and R.

Results

The positivity rates for SARS-CoV-2 were 8.2% in Washington State outpatient clinics, 8.4% in Seattle outpatient clinics, and 14.4% in Seattle emergency departments. Positivity rates were higher in males than in females and peaked in both Seattle and Washington State locations around March 28-29, 2020. Testing volumes steadily increased during the first half of March and peaked around March 12-13, 2020 for outpatients.

Discussion

SARS-CoV-2 infections in outpatient clinics in Washington State and Seattle Emergency Departments peaked in late March and have been declining. This trajectory aligns with the implemented social distancing guidelines and stay-at-home orders. Testing criteria did not change during the study and testing volume did not increase, indicating that positivity is not attributed to expanded testing. As this is a limited subset of the Washington population, the results may not be representative of the entire state.

Question

Are there epidemiologic or clinical characteristics that can be used to predict the course of COVID-19 and needs of individual patients?

Findings

10 independent predictors were used to develop a risk score (COVID-GRAM) that predicts illness severity. Predictors are chest radiography abnormality, age, hemoptysis, dyspnea, unconsciousness, number of comorbidities, cancer history, neutrophil to lymphocyte ratio, lactate dehydrogenase (LDH), and direct bilirubin.

Methods

• This retrospective study utilized records from 1590 patients with confirmed COVID-19 throughout China between November 12, 2019 and January 31, 2020

• Severe COVID-19 was defined based on the American Thoracic Society guidelines for community-acquired pneumonia

• Critical COVID-19 illness was defined as ICU admission, invasive mechanical ventilation or death

• LASSO and logistic regression was applied to 72 variables

Results

• Patient Characteristics

  • Of the 1590 patient sample 24 (1.5%) had severe disease on admission

  • 131 patients (8.2%) developed critical COVID-19

  • The overall mortality rate was 3.2%

  • Mean (SD) age was 48.9 (15.7) years

  • 25.1% had at least one coexisting condition reported

  • Fever, dry cough and fatigue were the most common symptoms

  • 71.1% of patients had an abnormal chest CT

• Predictor Selection

  • LASSO and logistic regression revealed 10 consistently significant variables that correlated with critical COVID-19

    1. CXR abnormality (OR, 3.39; 95% CI, 2.14-5.38; P < .001)

    2. Age (OR, 1.03; 95% CI, 1.01-1.05; P = .002)

    3. Hemoptysis (OR, 4.53; 95% CI, 1.36-15.15; P = .01)

    4. Dyspnea (OR, 1.88; 95% CI, 1.18-3.01; P = .01)

    5. Unconsciousness (OR, 4.71; 95% CI, 1.39-15.98; P = .01)

    6. Number of comorbidities (OR, 1.60; 95% CI, 1.27-2.00; P < .001)

    7. Cancer history (OR, 4.07; 95% CI, 1.23-13.43; P = .02)

    8. Neutrophil-to-lymphocyte ratio (OR, 1.06; 95% CI, 1.02-1.10; P = .003)

    9. Lactate dehydrogenase (OR, 1.002; 95% CI, 1.001-1.004, P < .001)

    10. Direct bilirubin (OR, 1.15; 95% CI, 1.06-1.24; P = .001)

  • A web-based calculator can be accessed here: http://118.126.104.170/

• Performance and Validation

  • The AUC of COVID-GRAM ranged between 0.82 and 0.87 (0.73-0.91) compared to the CURB-6 model applied to the same sample AUC of 0.75 (0.70-0.08)

  • 710 COVID-19 patients with similar characteristics to the original cohort but not included in the original cohort were used to validate the COVID-GRAM risk score

  • The AUC for COVID-GRAM for this cohort was 0.88 (95% CI, 0.84-0.93)

Limitations

• The sample size and validating cohort were relatively small to develop risk score

• All patient records used in the study are from China, possibly limiting generalizability

Key Points

• • Cases reviewed for two weeks between March 23 to April 7, 2020 at Mount Sinai Health System.

  • 5 cases of large vessel stroke in patients less than 50 years of age were reviewed in patients with SARS-CoV-2.

  • During this pandemic, Mount Sinai has treated 5 patients younger than 50 years of age with large-vessel stroke in two weeks. In comparison, Mount Sinai treats 0.73 patients younger than 50 years of age with large-vessel stroke before this pandemic.

  • Coagulopathy and vascular endothelial dysfunction have been proposed as complications of COVID-19 and could contribute to this rise in large-vessel stroke in young patients.

Summary

In this letter, the authors report 5 cases of Guillain-Barre syndrome (GBS) after onset of COVID-19. Three patients had an acute onset of axonal variant GBS with a demyelinating process in two patients 5-10 days after the onset of COVID-19 symptoms. This case series supports an association between GBS and coronavirus infections such as COVID-19.

Background

GBS is a rapidly progressing demyelinating disorder in which the immune system attacks the nervous system. GBS is often triggered by infection. Weakness and tingling of extremities progresses to eventual paralysis of the whole body. The disorder can be life-threatening, developing into breathing muscle weakness requiring mechanical ventilation.

Methods

Case series of 5 patients reported to have GBS after onset of COVID-19 between February 28 and March 21, 2020 in three Northern Italian hospitals.

Results

• • First symptoms: lower-limb weakness and paresthesia (4 patients), facial diplegia followed by ataxia and paresthesia (1 patient).

  • Evolution of symptoms: tetraparesis or tetraplegia (4 patients), mechanical ventilation (3 patients)

  • Interval between symptoms of COVID-19 and first symptoms of GBS: 5-10 days

  • COVID-19 diagnostics: Positive nasopharyngeal swabs for SARS-CoV-2 at the onset of neurologic syndrome (4 patients), positive serologic test only (1 patient).

  • CSF diagnostics: normal protein level (2 patients), WBC <5 (5 patients), all patients negative for antiganglioside antibodies (3 patients tested), all patients negative for RT-PCR for SARS-CoV-2 in CSF

  • Electrophysiological studies: low muscle action potential amplitudes, prolonged motor distal latency (2 patients), fibrillation potentials (4 patients).

  • MRI with gadolinium: enhancement of caudal nerve roots (2 patients), enhancement of facial nerve (1 patient), no signal changes in nerves (2 patients).

  • Treatment: all five received intravenous immune globulin (IVIG), 2 patients received second course of IVIG, 1 patient started plasma exchange

  • 4-week follow-up: 2 patients remained in ICU with mechanical ventilation, 2 patients undergoing physical therapy, 1 patient discharged able to walk independently.

Conclusions

• • All findings consistent with axonal variant GBS in 3 patients and demyelinating process in 2 patients.

  • The interval of 5-10 days between onset of viral illness and first symptoms of GBS is similar to other infectious GBS presentations.

Summary

This paper summarizes the neurological manifestations of patients with COVID-19, including acute cerebrovascular events, impaired consciousness, and muscle injury. Neurologic symptoms were seen in ⅓ of patients with COVID-19 and were more common in patients with severe infection according to their respiratory status.

Background

The COVID-19 pandemic literature has described typical clinical manifestations including fever, cough, diarrhea, and fatigue. There has not been a report of patients with COVID-19 and neurologic manifestations.

Methods

Retrospective, observational case series. Data collected between January 16 and February 19, 2020 at select centers in Wuhan, China. Three categories of neurologic manifestations were reported:

1. Central nervous system: dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, seizure

2. Peripheral nervous system: taste impairment, vision impairment, nerve pain

3. Skeletal muscular injury

Results

• • 214 consecutive hospitalized patients with lab-confirmed SARS-CoV-2 infection reported in this study.

  • 58.9% (126 patients) had non-severe infection and 41.1% (88 patients) had severe infection according to their respiratory status.

  • 36.4% (78 patients) overall had neurologic manifestations.

  • Patients with more severe infection had more neurologic manifestations such as acute cerebrovascular disease (5.7% vs. 0.8%), impaired consciousness (14.8% vs. 2.4%), and skeletal muscle injury (19.3% vs. 4.8%).

Conclusions

• • Many patients with COVID-19 have neurologic manifestations.

  • Most neurologic manifestations occurred early in the illness (the median time to hospital admission was 1-2 days).

  • During the COVID-19 pandemic, clinicians should suspect SARS-CoV-2 infection as a differential diagnosis when seeing patients with neurologic manifestations.

Limitations

• • Most symptoms were a patient’s subjective description due to avoidance of invasive diagnostic procedures.

  • Small study population (214 patients) and only one city (Wuhan) could cause biases in clinical observation.

  • Data extracted from electronic medical records; mild neurologic manifestations could have been missed (ex. taste and smell impairment).

  • No clinical outcomes of neurological manifestations could be reported.

There has been much evidence of COVID-19 coagulopathy and thrombosis associated with morbidity and mortality, however, most studies on this topic have been retrospective or limited by small sample size

Methods

• Patients admitted to one of 4 intensive care units at two French tertiary hospitals for ARDS due to COVID-19. Medical history, symptoms and laboratory values were collected prospectively

• Characteristics of COVID-19 patients were compared to a historical, prospective cohort of non-COVID-19 ARDS patients collected between 2014 and 2019

  • History of thromboembolic events was not significantly different between COVID-19 and non-COVID-19 ARDS patients before or after cohort matching

Results

• Patients

  • 150 COVID-19 patients were recruited

  • Median age was 63 and 81.3% were male

  • Median length of stay was 9.6 days

  • Mortality rate was 8.7%

    • 67.3% of the cohort was still intubated at the date of analysis

• Thrombotic, Ischemic and hemorrhagic complications

  • A clinically significant thrombotic event was diagnosed in 42.7% of patients COVID-19, ARDS patients

    • 25% of these were pulmonary embolism

    • 2.7% experienced ischemic or hemorrhagic stroke

    • 18.7% experienced circuit clot (all of these patients were on dialysis)

      • This represented 96.6% of patients on dialysis

    • 8% of patients were on ECMO and 2 of these patients (1.3% of COVID-19 patients) experienced thrombotic occlusion of the pump

    • One patient experienced acute limb ischemia

    • 3.3% of patients experienced mesenteric ischemia

  • 2.7% experienced hemorrhagic complications

• Coagulation Disorders

  • Only 2.7% of patients met criteria for JAAM-DIC and all had normal ISTH scores

  • Von Willibrand factor (vWF) activity and antigen, and factor VIII were increased

  • 50 of 57 patients (87.7%) had positive lupus anticoagulant during ICU stay

• Comparing COVID-19 ARDS patients with non-COVID-19 ARDS patients

  • 77 COVID-19 patients were matched with 145 non-COVID-19 patients such that sex, age, medical history, organ failure and severity scores, PaO₂/FiO₂ ratio, anticoagulant treatment at baseline and ECMO support after matching were not different between groups

  • After matching, more thrombotic complications were diagnosed in COVID-19 ARDS patients than matched controls (11.7% vs 4.8%)

    • With significantly more pulmonary embolisms in the COVID-19 group 11.7% vs 2.1%, p = 0.008

  • PT, Antithrombin, fibrinogen and platelets were significantly higher in COVID-19 patients than in matched controls

  • aPTT and D-dimer were significantly lower in COVID-19 patients than in matched controls

• Compared to the general population

  • The odds ratio (OR) of thromboembolic event was 2.7 [1.1-6.6], p = 0.028 and 9.3 [2.2-40], p = 0.003 for pulmonary embolism in COVID-19 patients with ARDS

Interpretation

• Patients with COVID-19 related ARDS are at increased risk of pathologic thrombosis, especially pulmonary embolism

• Higher than normal anticoagulation parameters should be considered

• Coagulation activation patterns in COVID-19 patients are different from patients with non-COVID-19 related ARDS indicating that mechanisms leading to coagulopathy may differ in COVID-19 patients

  • The pattern of high vWF and lower than expected D-dimer indicated endothelial inflammation

Introduction

• ACE2 receptor, a membrane-bound aminopeptidase that is ubiquitous in the heart, lungs, and other tissues serves as an entry way for coronaviruses into the cells

• ACEi and ARBs serve as first-line medications in disease conditions such as HTN, HF, CKD, post-MI states and increase expression of ACE2

• The hypothesis that the use of ACEi and ARBs may modify a person’s risk and severity of SARS-CoV-2 infection is yet to be validated

Objective

To analyze the association between the use of RAAS blockers and the risk of COVID-19

Methods

• Case-control study

• Demographic: Residents of Lombardy, Italy (40 years or older) who were beneficiaries of the Regional Health Service

• 6292 patients were counted as case patients

  • Selected from COVID-19 cases from February 21 to March 11

  • 617 patient who were placed on mechanical ventilation or died were categorized as critical or fatal infection; the rest were categorized as mild-to-moderate infection

• Drugs that act through the RAAS pathway that were administered during this period were noted including (ACEi, ARB, renin inhibitors, sacubitril-valsartan)

  • Their use as monotherapy or in combination therapies were accounted for

  • Other non-RAAS drugs were taken into account including lipid-lowering drugs, oral hypoglycemics, NSAIDs e.t.c.

• Analysis:

  • The between-group relative difference in clinical features and drug exposures was used for comparison

  • Crude and adjusted estimates for effects of antihypertensive therapy were obtained

  • To test the hypothesis that exposure would affect severity of illness:

    • Analyses were limited to patients in the critical or fatal infection category

    • Sex and age stratification were done as secondary analyses

Results

• Control could not be found 20 patients

• 6272 case patients were matched to 30,759 controls

  • 1:5 matching was used for 6015 case patients

  • 257 case patients had < 5 controls

  • Mean (±SD) age of case and control was 68±13 years

  • 37% were women

• ACEi and ARBs and other antihypertensives (antiHTNs) were used more frequently in case than in control

  • Percentage of patients who received these medications in case vs control include:

    • ARBs - case 22.2% vs control 19.2% (13.3% relative difference)

    • ACEi - 23.9% vs 21.4% (relative difference (10.5%)

    • Loop diuretics - 13.9% vs 7.8% (relative difference 43.6%)

    • Mineralocorticoid-receptor antagonists 3.8% vs 2.4% (relative difference 37.1%)

• Case patients used more combination of antiHTN drugs and experienced more frequent hospitalizations than controls

Conclusions

• The use of ACEi and ARBs was not significantly associated with the risk of COVID-19

  • The same is true for calcium-channel blockers, beta-blockers, and diuretics

• There was an increased risk of COVID-19 among patients who use loop diuretics and other non antiHTNs (insulin, antiplatelet agents, anticoagulants, immunosuppressant drugs and drugs used for respiratory disease)

• There was no statistical evidence of independent association between the use of antiHTNs and risk of COVID-1.

• There was an increased risk of COVID-19 in patients with previous hospitalizations for cardiovascular and cardiovascular diseases

• These findings were similar in men and women as well as in younger and older individuals

• No statistical evidence of an independent relationship between RAAS blockers and the susceptibility to and severity of COVID-19 in humans was found

Strengths

• Large sample size

• Well-matched control groups

• Access to previous hospitalizations, and prescribed drugs to outpatients

Limitations

• Information on drugs is limited to only prescriptions and none on actual consumption

• There was no information on drugs that were purchased privately by patients and those prescribed after December 31. 2019

  • Private purchase of drugs are rare however

• Results only include doses of RAAS blockers used in Italian medical practice

• Control group might have included people with COVID as the general public were not tested

• Confounder effect might have skewed results

• Results are applicable to only white populations and cannot be extrapolated to other races

Summary

Recipients of Kidney-transplant seem to be particularly susceptible to severe COVID-19 infection as a result of chronic immunosuppression and other comorbidities. A high early mortality of 28% at 3 weeks was reported when compared to 1 to 5% mortality among the general population who were tested and 8 to 15% mortality among patients >70 years.

Evidence from Montefiore Medical Center

• 36 consecutive kidney-transplant recipients who tested positive for COVID-19 between March 16 and April 1 were identified

  • 72% (26 recipients) were male, median age was 60 years (range 32 to 77)

  • 39% (14) were black, 42% (15) were hispanics

  • 75% (27) received a deceased-donor kidney

  • 94% (34) had hypertension, 60% (25) had diabetes mellitus, 36% (13) had a history of smoking, 17% (6) had a heart disease

  • 97% (35) were on tacrolimus, 94% (34) were on prednisone, 86% (31) were on mycophenolic acid or mycophenolate mofetil

• Most common symptoms experienced:

  • Fever in 58% (21 patients)

  • Diarrhea in 22% (8)

• Disease severity:

  • 22% (8) were in stable conditions and monitored at home; 78% (28) were admitted to the hospital

  • 96% (27) of the hospitalized patients had imaging consistent with viral pneumonia

  • 39% (11) were placed on mechanical ventilation; 21% (6) got renal replacement therapy

• Lab results of the 28 hospitalized patients:

  • Lymphopenic in 79% (22 patients)

  • Thrombocytopenia in 43% (12)

  • Low CD3 cell counts in68% (19); low CD4 in 71% (20); low CD8 in 29% (8)

  • Inflammatory markers:

    • Elevated ferritin levels >900 ng in 36% (10)

    • Elevated C-reactive protein levels >5 mg/dL in 46% (13)

    • Elevated procalcitonin levels >0.2 ng/mL in 43% (12)

    • Elevated D-dimer levels >0.5 μg/mL in 57% (16)

• Therapeutic management employed:

  • Immunosuppressive management

    • Withdrawal of antimetabolite in 86% (24 of 28)

    • Withholding of tacrolimus in 21% (6) who were severely ill

  • Hydroxychloroquine was administered to 86% (24 of 28)

  • Apixaban was administered to patients with D-dimer >3.0 μg/mL

  • CCR5 inhibitor (leronlimab) was given to 6 patients on a compassionate-use basis

  • IL-6 receptor antagonist (tocilizumab) was given to 2 patients

Outcomes

• • Follow-up - median 21 days (range, 14 to 28)

  • 28% (10 of 36 total kidney-transplant recipient) and 64% (7 of 11) intubated patients) died

  • 2 of 8 at home patients died and both received antithymocyte globulin with the past 5 weeks

The extreme range of COVID-19 severity make it a challenge to identify, predict and manage. This article reviews the presentation and management of patients with mild SARS-CoV-2 infection

Strategies and Evidence

Transmission

• • SARS-CoV-2 is primarily transported via respiratory droplets

    • Virus may be aerosolized in circumstances such as singing, intubation and with the use of nebulizers

  • Virus may persist on inanimate surfaces for days

  • Likelihood of transmission decreases when people remain more than 2 meters apart

  • Fecal oral spread has not been documented

  • Individuals may be infectious 1 to 3 days prior to symptom onset

    • Up to 50% of transmission may be attributable to presymptomatic individuals

  • Patients with severe disease may shed the virus for longer than those with mild disease

Clinical Manifestations

• • Median incubation period is 4 to 5 days

  • 95% of those who are symptomatic will have symptoms within 11.5 days of infection

  • Symptoms include fever, cough, sore throat, malaise, myalgia, nausea, vomiting and diarrhea

  • Shortness of breath is suggestive of worsening disease

  • Risk factors for complication include age > 65 years, cardiovascular disease, chronic lung disease, hypertension, diabetes and obesity

  • Common laboratory findings include lymphopenia and elevated D-dimer, lactate dehydrogenase, C-reactive protein and ferritin

  • Findings associated with poor outcome include increased white cell count with lymphopenia, prolonged PTT and elevated liver enzymes, lactate dehydrogenase, D-dimer IL-6, C-reactive protein and procalcitonin

  • Ground glass opacifications on chest imaging are typical if present

Diagnosis

• • RT-PCR assay of a nasopharyngeal swab is the standard for viral detection

  • Sensitivity is high but the rate of false negatives in undetermined

    • Repeat testing is warranted if clinical suspicion is high but testing is negative for SARS-CoV-2

  • If nasopharyngeal swab cannot be obtained, the CDC recommends oropharyngeal swab

    • Use of lower respiratory tract specimens and saliva are being validated

    • Sputum production (coughing) for testing purposes is not recommended because of aerosolization

  • Self-collection from the anterior nares is an acceptable form of testing

Evaluation

• • According to initial data from China, 81% of SARS-CoV-2 infection is mild or moderate

  • Mild disease is typically self-resolving and can be managed at home

  • Patients with mild COVID-19 and risk factors (above) should be monitored closely at home for disease progression

  • If disease progresses patients should be tested for other respiratory pathogens

  • Hospitalization is warranted for those with moderate of severe illness

  • Indicators of severe disease are

    • Tachypnea: >30 breaths per minute

    • Hypoxemia: Oxygen saturation < 93% or PaO₂/FIO₂ < 300

    • Lung infiltrates: > 50% of lung field

  • Chest radiography is the recommended initial imaging modality

    • Chest CT is discouraged except when indicated

Management of Mild or Moderate COVID-19

• • The mainstay of treatment is supportive and there are many clinical trials evaluating treatment

  • Hydroxychloroquine and Chloroquine with or without Azithromycin

    • These drugs demonstrated vitro activity against SARS-CoV-2 and have known anti-inflammatory effects

    • Some initial clinical trials have shown improved viral clearance with treatment while others have not found any benefit

    • Patients must be monitored for adverse effects such as QTc prolongation in those on Azithromycin and Hydroxychloroquine

  • Remdesivir: An inhibitor of RNA-dependent RNA polymerase

    • In vitro anti-SARS-CoV-2 activity has been demonstrated and case series have shown benefit

    • There is an ongoing phase 3 clinical trial

  • Immunomodulation: Glucocorticoids, convalescent plasma and anti-cytokine therapy are under investigation

Use of Concomitant Medications in People with COVID-19

• • There is no clinical data that ACE inhibitors or ARBs alter the course of COVID-19

    • It is recommended that patients continue ACE inhibitors or ARBs

  • There is no consistent data supporting a deleterious effect of NSAIDs

  • Glucocorticoids are not recommended for the treatment of COVID-19

Infection Control and Prevention

• • PPE should include isolation gown, gloves, face mask and eye protection

    • N95 respirator is recommended by the CDC

  • Enhanced protection is required in the setting of aerosol-generating procedures

  • Universal droplet precautions for all initial patient encounters is warranted

Areas of Uncertainty

• Prevalence of asymptomatic and presymptomatic COVID-19 cases in the community

• The extent to which fomites and aerosols contribute to transmission

• Whether infection confers complete immunity

• Whether serologic testing can be used to confirm past infection and recovery

Boston Health Care for the Homeless Program and public health agencies established a system of symptom screening, testing, referrals, isolation and treatment for homeless individuals who tested positive for SARS-CoV-2. A large number of positive cases at one large homeless shelter prompted testing of all residents described below.

Methods

• Residents diagnosed with COVID-19 on or prior to April 3 (n=22) had been removed from the shelter and were excluded from the study

Results

• All (n=408) residents underwent symptom screening and RT-PCR testing for SARS-CoV-2 infection

  • Mean age was 51.6 years and 71.6% were men

  • 12.2% reported symptoms, cough being the most common

  • 87.8% were asymptomatic

• 36% of residents tested positive for SARS-CoV-2

  • 84.4% of those who tested positive were men

  • 64.4% of those who tested negative were men

  • Of those who tested positive symptoms were uncommon

    • cough 7.5%, shortness of breath 1.4% and fever 0.7%

    • 87.8% were asymptomatic

Interpretation

• These results support a high burden of asymptomatic COVID-19 cases

• Authors suggest PCR testing of all shelter residents

• The proportion of residents who later developed symptoms is unknown

• A report released by the MMWR summarizing the prevalence of COVID-19 in 19 homeless shelters across 4 cities supports these results

Significance

A potential complication of severe COVID-19 pneumonia to be aware of is consolidation followed by mediastinal emphysema, bullae formation, and pneumothorax development. These complications arise independent of mechanical ventilation which has a known complication of emphysema and pneumothorax. Spontaneous pneumomediastinum is uncommon in viral pneumonia but does have an association with severe acute respiratory syndrome (SARS)-related pneumonia.

Background

There are few reports on chest CT findings of complications arising from severe COVID-19 pneumonia. This article reviews a case of COVID-19 pneumonia with mediastinal emphysema, giant bulla, and pneumothorax.

Case:

38-year-old male initially presented with fever, decreased lymphocyte count, and positive SARS-CoV-2 RT-PCR. He subsequently developed higher fevers and cough, and was initiated on high-flow nasal cannula oxygen therapy. Initial CT showed ground-glass opacities in the left lower lobe. Over the next 10 days, the lesions increased in extent and density; they progressed to a consolidation. The patient developed chest tightness, palpitation, dyspnea, and severe hypoxemia. He was diagnosed with acute respiratory distress syndrome (ARDS) as his symptoms deteriorated and was re-imaged. The CT did not reveal ARDS and instead revealed mediastinal emphysema. After 15 days of supportive treatment, chest CT showed improvement in pulmonary lesions, disappearance of mediastinal emphysema, but development of a giant bulla. The final follow-up CT scan revealed resolving bullae, but new findings of a small pneumothorax and pleural effusion. This patient did not have a history of pneumothorax, underlying pulmonary disease, or history of smoking. Of note, this patient did not receive mechanical ventilation, which is well-known to have mediastinal emphysema and pneumothorax as complications.

Conclusions

The most common CT finding in early stage COVID-19 pneumonia is ground-glass opacities in the subpleural regions of the lower lobes. This is attributed to alveolar swelling, exudation infiltrates, and inflammation. A potentially severe progression of this disease includes confluence and consolidation, emphysema, bullae, or pneumothorax. This may indicate that the diffuse alveolar injury in severe COVID-19 pneumonia makes alveoli more prone to rupture, particularly with a pronounced cough. This finding has been previously recorded in SARS-related pneumonia.

Follow-up correspondence

A similar occurrence of pneumomediastinum with COVID-19 pneumonia was reported a month later in a 36-year-old female. She also did not receive mechanical ventilation. The correspondence found that once pneumomediastinum appears, the patient’s condition was considered serious with worse prognosis. Unfortunately, this patient succumbed to the illness two days later.

Methods

• There were 89 residents on the date of the first positive test for SARS-CoV-2, March 3, 2020

• 76 residents consented to study participation

  • Mean age was 78.6±9.5 years

Results

• 48 (63%) of residents tested positive 10 days after the first positive test

  • Of these patients 35% reported fever, cough and/or shortness of breath

  • 8% reported atypical symptoms such as malaise, confusion, rhinorrhea, sore throat or dizziness

  • 56% reported no new symptoms

    • Of these residents, 89% reported symptom onset within 7 days of testing positive

    • The most common symptom was fever (71%)

• 57 residents (64%) tested positive for SARS-CoV-2 infection 23 days after the first positive test

  • 11 of the 57 residents were hospitalized

  • 15 had died (26% mortality)

• High viral loads were detected and viable virus was cultured from patients with and without symptoms

  • There was no correlation between viral load and symptom onset

• Doubling time was estimated to be 3.4 days

  • Doubling time was estimated to be 5.5 days in the surrounding community

• By March 26, 26 staff members reported positive tests for SARS-CoV-2 infection

Interpretation

• Doubling time was faster in this skilled nursing facility than in the community

• Asymptomatic infection and spread of SARS-CoV-2 likely accounts for a large proportion of viral spreading

• Staff likely contribute to viral spreading

• Underlying disease, immunosenescence and cognitive impairment make symptom-directed testing less reliable

Significance:

This study describes the clinical characteristics and outcomes of patients with COVID-19 hospitalized in one New York health care system. Patients who were older, men, and with preexisting hypertension and/or diabetes were more likely to be hospitalized. There remains a high mortality rate among ventilated patients (24.5%).

Background:

There is currently limited information describing the presenting characteristics and outcomes of US patients hospitalized for COVID-19. This study aims to highlight the clinical outcomes during hospitalization (mechanical ventilation, kidney replacement therapy, death), demographics, baseline comorbidities, presenting vital signs, and test results.

Methods:

Case series of patients hospitalized with COVID-19 in 12 hospitals within the Northwell Health system in New York. This study was limited to dates between March 1, 2020 and April 4, 2020. Only patients with confirmed SARS-CoV-2 infection via RT-PCR of nasopharyngeal samples were included.

Results:

5700 patients were included. Only 2634 patients were included in the outcomes data.

• • Common comorbidities: hypertension (56.6%), obesity (41.7%), and diabetes (33.8%)

  • Presenting vital signs: febrile (30.7%), respiratory rate > 24 breaths/min (17.3%), received supplemental oxygen.(27.8%)

  • Hospitalization course: ICU (14.2%), invasive mechanical ventilation (12.2%), kidney replacement therapy (3.2%), death (21%)

  • Mechanical ventilation prognosis: discharged alive (3.3%), death (24.5%), continued to be hospitalized (72.2%)

  • Discharge: post-discharge follow-up time was 4.4 days, 2.2% of discharged patients were readmitted (median time to readmission was 3 days)

Conclusions:

• • Older persons, men, and preexisting hypertension and/or diabetes were more prevalent in this hospitalized patient population.

  • Mortality rates are lower than case series in China, possibly due to differences in thresholds for hospitalization (though this study is limited by time and requires a longer-term study).

  • A high mortality rate among ventilated patients continues to exist and is similar to smaller case series in the US.

Limitations:

• • Most patients in the study were still in the hospital (72.2%). True mortality rates cannot be determined until “discharge.”

  • Only New York metropolitan area and in one hospital system.

  • Clinical outcome data was only available for 46.2% of admitted patients, which could bias the study.

Significance:

This small and very limited case series observes 25 asymptomatic patients who had viable exposures to COVID-19 and subsequently tested positive on RT-PCR. The majority of the asymptomatic carriers were young males with a blood type O (though this blood type is prominent in Asian countries). One-third of these asymptomatic patients developed mild symptoms at follow-up. Chest CT proved to be valuable in diagnosing 96% of patients. After early isolation of asymptomatic cases, a follow-up CT showed all patients to have decreased lung involvement. No conclusions were made about the chosen medical therapy.

Demographics:

22 of 25 patients took care of confirmed COVID-19 family members. The other 3 were staff involved with cleaning medical waste and in transportation in the hospital, ⅔ men, average age of 42 (young), majority with blood type O

Results:

• CT findings: 24 of 25 had abnormal CT findings in lungs.

• Disease Course: 16 recovered without symptoms, 9 developed mild cough and/or other symptoms and were medically treated.

• Interventions: all 9 symptomatic patients received 500mg chloroquine phosphate BID x 7 days & 200mg Abidol TID x 10 days.

• Follow-up CT: performed 7-30 days after isolation, all 24 patients had decreased involvement, 1 patient did not have radiological findings to begin with.

This case study reports that SARS-CoV-2 does not appear in the amniotic fluid of 2 pregnant women with confirmed SARS-CoV-2 infection in the first trimester of pregnancy

• Patient 1 was a 34 year old female admitted for COVID-19 on January 30 at 8 weeks gestation and discharged on February 13

• Patient 2 was a 27 year old female who tested positive for SARS-CoV-2 on February 12 and was admitted for COVID-19 on February 18 and discharged on February 28

• Both patients had positive SARS-CoV-2 serum IgG antibodies and negative SARS-CoV-2 RNA throat swabs on March 23 and 26

• Amniotic fluid samples were collected on March 26

  • SARS-CoV-2 RNA was not detected in amniotic fluid

  • SARS-CoV-2 IgM and IgG were not detected in amniotic fluid

Interpretation

• These cases contribute to our understanding of SARS-CoV-2 in pregnant women

• Viral transmission into the amniotic fluid cannot be ruled out by these findings but other studies suggest that vertical transmission does not occur

This study is one of the first to describe patient characteristics and hospital course in New York City and highlights similarities and differences between case series conducted in other countries

Methods

• This retrospective case series includes 393 patients 18 years and older with nasal swab RT-PCR confirmed COVID-19

• Patients were consecutively admitted at one of two hospitals in Manhattan between March 3 (date of first positive case) and March 27

Results

• Median age was 62.2 years and 60.6% were male

• 35.8% of patients had obesity

• The most common presenting symptoms were cough (79.4%), fever (77.1%) and dyspnea (56.5%)

  • Gastrointestinal symptoms were more prominent in this study than in larger case series conducted in China

  • 23.7% experienced diarrhea and 19.1% experienced nausea and vomiting

• 90% of patients had lymphopenia and 27% had thrombocytopenia

• Respiratory failure requiring invasive mechanical ventilation developed in 33.1% of patients

  • These patients were more likely to be male, obese and to have elevated liver function and inflammatory markers (including C-reactive protein and procalcitonin)

  • Patients were more likely to require vasopressor support and first time renal replacement therapy, and to experience atrial arrhythmia

  • Of these patients, nearly one-third did not require invasive mechanical ventilation in the first 3 hours after presentation to the ED

• 10.2% of patients had died and 66.2% were discharged prior to April 10, 2020

In this study a sample of patients from hospitals around China were used to create a model to predict probability of survival during admission

• This retrospective study included 1590 patients with positive RT-PCR or high throughput sequencing tests for SARS-CoV-2 admitted to one of 575 hospitals in China before January 31

  • This cohort represented 13.5% of infected patients in China

• By January 31 there were 50 fatal cases of COVID-19 reported

  • Case fatality 3.14%

    • Case fatality was 8% for patients 70-79 years old

  • Median age was 69 years old and 60% were male

  • Median duration from initial treatment to death was 11 days

  • The most common symptom was fever (87.5%)

  • The incidence of dyspnea was significantly higher in patients who died than in those who did not

    • Whether dyspnea was present on admission is not stated

  • Most common lab abnormalities in fatal cases were elevated CRP (100%), lymphopenia (97.6) and elevated lactate dehydrogenase (91.4%)

    • Lab abnormalities were more prominent in fatal cases compared to survivable cases

  • Invasive mechanical ventilation was performed for 62.5% of fatal cases and 10.8% received ECMO

  • ARDS was the most common complication of fatal cases (90%)

• A multivariate regression model demonstrated some independent predictive factors for fatal outcome including

  • Age >65 (with an increased predictive confidence for those > 75 years old), coronary artery disease, cerebrovascular disease, dyspnea, procalcitonin > 0.5ng/mL and AST > 50 U/L

  • Sex was not an independent predictive factor

• Results were used to create a nomogram to predict survivability at 14, 21 and 28 days

News:

NIH begins a new, nationwide study to determine how many adults without a confirmed COVID-19 history possess antibodies to SARS-CoV-2.

• Cotton-swab based molecular testing determines active infection, but does not indicate whether a person has been previously infected with SARS-CoV-2

• The presence of antibodies in the blood indicates a prior infection

Study Aims:

1. Provide insights on undetected spread of coronavirus, and which communities and populations are most affected

2. Assess the impact of current public health measures

Methods:

Investigators will analyze blood samples for anti-SARS-CoV-2 S protein IgG and IgM.

• Healthy volunteers >18 from anywhere in the U.S. can participate

• Volunteers cannot have a confirmed COVID-19 history or exhibit current symptoms consistent with COVID-19

• Study participants will attend a virtual clinic visit, complete a health assessment questionnaire, provide basic demographic information, and have blood drawn (participants from NIH Bethesda campus) or participate in at-home blood collection kits (other participants)

More Information:

People interested in joining this study should contact clinicalstudiesunit@nih.gov

For more information on the COVID-19 Pandemic Serum Sampling Study Launch, see the Questions and Answers.

Background:

Coronavirus is an enveloped positive-sense RNA virus that targets epithelial cells and causes respiratory infection, including severe acute respiratory syndrome (SARS) and acute exacerbation of chronic bronchitis (AECB). The novel SARS-CoV-2 coronavirus was discovered in Wuhan, China in 2019 and is able to infect multiple host species. Consequences of the disease include dyspnea, hypoxemia, acute respiratory distress syndrome (ARDS), septic shock, and multiple organ failure. Associated hematology results of these patients show lower lymphocytes, higher lactate dehydrogenase (LDH), higher creatine kinase (CK), higher C-reactive protein (CRP), and inflammatory factors. These findings have been associated with the severity of the disease. The purpose of this study is to determine if urine biochemical markers can be effectively measured to predict the severity of COVID-19.

Methods:

45 healthy controls and 119 patients diagnosed with COVID-19, further subgrouped by disease severity, were enrolled in the study. 20 mL of midstream urine samples was obtained from each subject the morning after admission. Occult blood, proteinuria, bilirubin, urobilinogen, potential of hydrogen (pH), specific gravity, ketone, urine glucose, nitrite, and leukocyte levels were tested using an automatic urine biochemical analyzer. Count data were analyzed using a chi-square test and normally distributed measurement data were analyzed using a two sample t-test. A p-value less than 0.05 indicates statistical significance.

Results:

Both blood and protein levels were significantly higher in patients with COVID-19 than in healthy controls. In addition, the differences in serum gravity and pH between groups was statistically significant. Positive rate of leukocyte was not significant between groups and indicates that the differences in blood, protein, specific gravity, and pH are caused by SARS-CoV-2 infection rather than bacterial infection. Therefore, these four parameters could be used for auxiliary differentiation of COVID-19 patients from healthy individuals. Furthermore, there were significant differences in glucose and protein between the different subgroups of patients with COVID-19. Glucose and protein was significantly increased in the severe and critical groups compared to the moderate group.

Significance:

Urine biochemical parameters are useful in identifying COVID-19, but also in evaluating progression in previously diagnosed patients.

Objective:

• This study aims to investigate the duration of viral shedding from discharged patients with severe COVID-19.

Methods:

• Enrolled 41 discharged patients with severe COVID-19 from Union Hospital of Tongji Medical College. Median age 58.0 yrs ranging from 17 yrs to 75 yrs; 22 males and 19 females. All patients had positive RT-PCR tests for COVID-19 nucleic acid following original hospital admission and COVID-19 diagnosis.

• Severe COVID-19 defined as at least one of the following: respiratory distress with respiratory rate >30 times/min; oxygen saturation ≤ 93% in resting state; PaO2/FiO2 of ≤300mmHg.

• Criteria for discharge included all of the following: normal temperature for greater than 3 days; resolved respiratory symptoms; improved acute exudative lesions on chest CT; 2 consecutive negative RT-PCR tests separated by at least 1 day.

• Patients separated into 2 groups: < 65 yrs, and ≥ 65 yrs.

• Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of throat swabs to assess viral shedding.

• Simple t test and Mann-Whitney U test was used to compare continuous variables.

Results:

• Duration of viral shedding:

  • Median 31.0 days from illness onset (IQR: 24.0-40.0 days)

  • Shortest duration 18 days; longest duration 48 days

  • No significant difference between male and female viral shedding time (p=0.33)

  • No significant difference between age < 65 yrs and age ≥ 65 yrs (p=0.75)

• Total time of illness (from illness onset to discharge)

  • Medan 40.0 days (IQR 32.0-46.0)

  • Shortest total time of 24 days; longest total time of 56 days

  • No significant difference in total time of illness between male and female patients (p=0.44)

  • No significant difference in total time of illness between age < 65 yrs and age ≥ 65 yrs (p=0.55)

Discussion:

• Patients with severe COVID-19 showed positive RT-PCR tests for SARS-CoV-2 RNA for median of 31.0 days after illness onset

• Previous studies showed detectable SARS-CoV-2 RNA for median of 20 days after illness onset

• Patients with severe COVID-19 may need longer duration of symptomatic and supportive treatments due to prolonged viral shedding

• No significant difference with duration of viral shedding or total time from illness onset to discharge between males and females or between those < 65 yrs and those ≥ 65 yrs

Limitations:

• Study limited to 41 patients

• Estimation of viral shedding limited by frequency of respiratory specimen collection and relatively low positive rate of SARS-CoV-2 RNA detection in throat swab

Epidemiological definition for further understand

Serial interval: The duration between symptom onset of successive cases in a transmission chain.

Key Learning Point:

If the serial interval for any given infection is short, this indicates that the transmission of the infection may have occurred before the individual presented with any symptoms, reducing the effectiveness of control measures such as isolation and contact tracing.

Summary

Temporal profiles of patterns of viral shedding in 94 COVID-19 positive patients and 77 infector-infectee transmission pairs were modeled. Findings showed that a significant portion (44%) of secondary cases were infected during the presymptomatic stage of the infector. Disease control measures should account for the substantial presymptomatic transmission likely occurring.

Methods

• Ninety-four patients with confirmed COVID-19 were moderately ill (febrile and/or positive respiratory symptoms and radiographic evidence of pneumonia).

• A total of 414 throat swabs obtained from these patients from symptom onset up to 32 days after symptom onset.

Results

• High viral load was detected until day 21, where there was a gradual decline to detection level.

• Based on 77 transmission pairs, the serial interval was estimated to have a mean of 5.8 days and a median of 5.2 days.

• Researchers inferred that infectiousness started 2.3 days before symptom onset and peaked at 0.7 days before symptom onset.

• The estimated proportion of pre-symptomatic transmission of 44%, using area under the curve models.

Discussion

• Substantial transmission potential before symptom onset likely exists, with viral shedding happening likely 2-3 days prior to the first appearance of symptoms.

• Contact tracing is likely more effective if the definition of contact tracing covers 2-3 days prior to symptom onset.

Between January 28^th and March 13^th of 2020, there were six COVID-19 recurrence cases in Shangqiu, Henan Province, China. Recurrence was determined by positive nucleic acid testing (RT-PCR). While four of the six cases were asymptomatic with positive nucleic acid tests, two cases had symptoms with positive tests.

Patient characteristics

• All patients were female.

• Ages ranged from 30-56 years (median: 45.2 years).

• Two of six patients had a pre-existing comorbidity: hypertension in one and chronic bronchitis in the other.

Two patients had symptoms with relapse of COVID-19.

• One patient had fatigue, expectoration, muscle soreness, and nausea. Temperature ranged from 36.5-36.8 degrees Celsius with recurrence of COVID-19. She was discharged on February 17^th, 2020, followed by a 2-week quarantine period at home. On February 26^th, 2020, she had a positive nucleic acid test.

• The second patient had a cough.

At initial discharge, patients with recurrence of COVID-19 had no significant differences in leukocytes, lymphocytes, neutrophils, platelets, and albumin from control cases.

Treatments included

• Recombinant human interferon α-1b/2b antiviral therapy

• Oral lopinavir/ritonavir

• Abidol

• Traditional Chinese medicine treatments

• Methylprednisolone

(It is not clear in the paper whether these treatments were used during the initial and/or recurrence case of COVID-19.)

The authors suggest a continued observation of discharged patients following COVID-19.

There is a growing body of evidence demonstrating that SARS-CoV-2 infects many organ systems including gastrointestinal epithelial cells and that fecal-oral transmission may pose a threat of continued spread

Methods

• In this retrospective study, fecal samples were tested for SARS-CoV-2 RNA in of 42 patients admitted to Zhongnan Hospital, China between January 20 and March 9, 2020

• All patients tested positive for SARS-CoV-2 via pharyngeal swab RT-PCR

Results

• The average age was 51 years old, 64% of participants were women and 40 percent of participants had comorbidities

• 66.7% of the sample population tested positive for fecal SARS-CoV-2

  • 21.4% of those with detectable fecal SARS-CoV-2 RNA experienced diarrhea while only 7.1% of those with a negative fecal test reported diarrhea

  • There was no correlation between fecal SARS-CoV-2 RNA and CT-scan findings, disease severity

• The median time from symptom onset to positive pharyngeal RT-PCR test was 6.5 days while the median time to positive stool test was 11 days

  • The median duration of positive fecal RT-PCR was longer in those with severe disease compared to those with mild disease (14 vs 8 days)

    • There was no significant difference between groups

Interpretation

• SARS-CoV-2 RNA is found in feces of some patients with COVID-19

  • Although correlations between GI symptoms and fecal SARS-CoV-2 RNA were observed, this study was limited by sample size

• It remains unclear whether the virus remains viable after passing through the GI tract

Background

• South Korea has recently had a rapid increase in COVID-19 cases, overwhelming clinics and emergency departments.

• In order to combat this, two innovative methods of COVID-19 have been implemented recently: Drive-Through and Walk-Through testing.

• These innovative methods allowed for safer public testing, further ensuring the safety of healthcare and government officials involved with the testing.

Testing methods:

Drive-through testing:

• Rapidly administered and conducted within 15 min with no need for the individuals being tested to get out of the care; minimal risk of contraction

• Examiners need level D-PPE; no need for repeated sanitation

• Testing conducted in open areas (e.g., empty parking lots, open range areas)

• Higher healthcare worker risk due to fatigue with extended PPE use outdoors

• Limited by weather/Car needed

Walk-through test (2 methods: positive pressure and negative pressure booth)

• Positive pressure booth:

  • Completed within 15 min; testee has to physically go to the booth

  • Booth walls separate testee from the healthcare worker, ensuring safety of both

  • Allows to test far more patients, with multiple operating booths

  • Healthcare staff is in one booth the whole time; no sanitation required after each test

• Negative pressure booth:

  • Similar to positive booth, except healthcare worker is outside the booth

  • Conducted in 20 min; requires sanitization after each use

  • Can test multiple individuals at once; further robustness of the method

Discussion/Implications:

• These new, innovative methods have allowed the healthcare system to dramatically increase the rate of COVID-19 testing.

• Well-designed booths and drive-through systems can accommodate high volume of individuals looking to get tested without overworking healthcare workers and exacerbating limited resources (PPE). Furthermore, they provide a safer outlet and encourage individuals to test.

• Rapid testing methods can serve as a model for other nations to effectively test for COVID-19 without exacerbating limited healthcare resources.

Summary:

• Affected patients with COVID-19 have been exhibiting atypical neurological symptoms as initial symptoms, such as:

1. Headaches

2. Cerebral hemorrhage

3. Cerebral infarction

• Of 214 cases, 78 had a neurological manifestation and 40 had to be placed in the intensive care unit (ICU) for severe neurological involvement.

Theories:

• SARS-CoV-2 requires ACE2 to invade respiratory epithelial cells. Following the infection, the expression and function of ACE2 is reduced. ACE2 signals normally reduce blood pressure. This leaves hypertensive patients that already have a low expression of ACE2, vulnerable to the induction of cerebral hemorrhage by SARS-Cov-2 infection.

• COVID-19 may cause an increase in D-dimers, leading to thrombotic vascular events such as cerebral venous and/or arterial infarctions.

Discussion:

• HCoV-OC43, another strain of coronavirus, has been previously shown to be detected in the CSF fluid of a child with acute demyelinating encephalomyelitis.

• SARS-CoV-2 has been reported to attack and damage the nervous system. Its RNA was detected in CSF.

Conclusion:

• Healthcare providers should be vigilant for neurological symptoms as the presenting symptoms of COVID-19. These patients with atypical presentation represent an important source for the spread of the disease.

Purpose:

• To determine the incidence of venous thromboembolism (VTE) in patients affected with severe SARS-CoV-2 pneumonia who end up in ICU, and analyze differences in patients with VTE vs those without VTE.

Background:

• Studies revealed that severe novel coronavirus pneumonia (NCP) has been associated with coagulopathy. Patients presenting with NCP who have concomitant coagulation dysfunction are likely to have a poor prognosis.

Method:

• This study enrolled 81 patients (44 females; mean age of 59.9; 33 had comorbidities; 35 had a history of tobacco use) who were diagnosed with NCP based on WHO guidelines and determined the severity of their disease.

• Patients were given antiviral and supportive care, no preventive anticoagulant and were evaluated using clinical examination, laboratory tests, chest CT, lower extremity venous doppler ultrasound and SARS-CoV-2 real-time reverse transcriptase PCR.

Results:

• 20 patients (25%) with severe NCP developed lower extremity venous thrombosis and 8 of those patients died. Contributing factors found in patients with VTE included older age, lower lymphocyte counts-especially T-cells, longer aPTT and higher levels of D-dimer.

• Older patients with other comorbidities are more susceptible to VTE due to poor immune function.

• Sepsis may be precipitated by severe SARS-CoV2 infection in NCP patients which can in turn trigger coagulation-activating inflammatory cytokines. Thus promoting a conducive milieu for the development of VTE.

• Incidence of disseminated intravascular coagulation (DIC) in dead NCP patients was 71.4% and sepsis is an important cause of DIC.

• Coagulaopathy and VTE were associated with poor prognosis in NCP patients.

• D-dimer level may be used to predict VTE as well as monitor responsiveness to anticoagulant therapy.

Limitations:

• This was a single-location, retrospective study, with a small sample.

• Some patients had not fully recovered and may have altered clinical outcomes.

Methods

Targeted testing:

• • 1924 individuals were tested for SARS-CoV-2 after presenting with symptoms of COVID-19 between January 31 and March 15, 2020 (early targeted testing)

  • An additional 7275 individuals underwent targeted testing between March 16 and March 31, 2020 (late targeted testing)

Population-screening:

• • Iceland began elective screening of asymptomatic and mildly symptomatic individuals in its capital between March 13 and April 1, 2020

    • 10,797 people were tested

  • 6782 Icelanders between the ages of 20 and 70 years were also randomly selected for testing

    • Individuals who tested positive for SARS-CoV-2 underwent contact screening to identify the source of infection and all contacts within the last 24 hours

    • Registered contacts were called and screened for symptoms

    • Those with symptoms were tested for SARS-CoV-2

      • 295 infectious contact-pairs identified by contact tracing were positively validated by viral sequencing

All SARS-CoV-2 RT-PCR tests were performed within 24 hours of sample collection

Results

Of people who underwent elective or random screening, 0.8% and 0.6% tested positive respectively

• • These rates remained between March 13 and April 1

Asymptomatic infection is nearly as prevalent as symptomatic infection

• • In random sample selection and elective screening (together referred to as the population-screening), 46.2% and 58.6% of those who tested positive reported symptoms respectively

  • 43% of participants in the population-screening who tested positive reported no symptoms

  • 29% of those who tested negative in the population-screening reported symptoms

In all groups, those who tested positive were older

• • In participants 20 years and younger there was a gradual increase in percent infection with age

  • No participant under 10 years old tested positive in the population-screening

The percentage of males who tested positive was greater in the population-screening (0.9% vs. 0.6%) and targeted testing (16.7% vs 11.0%)

• • Odds ratio of 1.55 (95%CI, 1.04 – 2.03) in the population-screening

  • More females than males were tested in all testing groups

643 SARS-CoV-2 samples were sequenced to identify mutations and assign haplotype

• • Haplotypes were used to create a median-joining network that matches haplotype, number of hosts and geographical region

    • The B1 haplotype appears to be the major strain circulating in the US

  • In Iceland, haplotype changed significantly between early and late targeted testing

    • This is likely a result of self-quarantining individuals who travelled from areas then classified as high-risk, like the Alps

  • Tracking the diversity of SARS-CoV-2 haplotypes over the month of March demonstrated a shift from travel related exposure to familial exposure to SARS-CoV-2

Viral genome sequencing confirmed contact tracing in 295 of 369 contact-pairs identified by contact tracing

Methods

• Nasopharyngeal RT-PCR testing for SARS-CoV-2 was performed in all pregnant women admitted for delivery at the New York-Presbyterian Allen Hospital and Columbia University Irving Medical Center

Results

• 215 pregnant women were tested between March 22 and April 4, 2020

• 4 (1.9%) women had symptoms of COVID-19 including fever

  • All 4 women tested positive for SARS-CoV-2

• 29 (13.7%) of 210 asymptomatic women tested positive for SARS-CoV-2

  • 87.9% of pregnant women with SARS-CoV-2 were asymptomatic

  • 3 (10%) of SARS-CoV-2 positive, asymptomatic women developed symptoms before discharge (median length of stay was 2 days)

Interpretation

• This brief correspondence highlights the importance of widespread testing

• It is unclear whether the rate of asymptomatic SARS-CoV-2 infection in pregnant women reflects rates in the general population

• Further testing for immunity of neonates born to mothers with SARS-CoV-2 infection is required to determine their immunity status and will inform postpartum practices, such as direct mother-baby contact

This article continues ongoing work to determine which biomarkers can inform prognosis for patients with COVID-19 infection.

Study Design

• Subjects were 76 patients admitted to the First Affiliated Hospital of Nanchang University (Nanchang, China) between January 21st and February 4th of 2020, all of whom were confirmed to have COVID-19 at admission.

• 30 cases were categorized as severe due to either respiratory distress, low oxygen saturation, low ratio of arterial oxygen partial pressure to fractional concentration of oxygen inspired air, or severe disease complications such as respiratory or other organ failure, septic shock, or need for mechanical ventilation. The remaining 46 cases were categorized as mild.

• Individual patient’s viral loads were determined via RT-PCR of nasopharyngeal swabs. The operational measurement of viral load was ΔCt, which refers to the difference between the threshold cycle of the patient’s sample and the threshold cycle of the reference. Higher ΔCt values indicate lower viral load, whereas lower ΔCt values indicate higher load.

• Patients’ ΔCt values were determined at various points through disease progression, with a subset of patients’ values being determined every day.

Results

• The mean viral load of severe cases, as determined through ΔCt, was approximately 60 times higher than the mean viral load of mild cases.

• ΔCt values of severe cases were significantly lower than those of mild cases at admission, and through the first 12 days following the onset of symptoms.

• In the subset of patients whose ΔCt values were measured every day (21 mild cases, 10 severe cases), mild cases had earlier viral clearance, with 90% testing negative by the 10th day following the onset of symptoms. All 10 severe cases were still positive on the 10th day.

Conclusion

• Viral load, as measured by RT-PCR, may serve as a marker of both disease severity and prognosis.

While the SARS-CoV-2 virus is primarily a respiratory virus, its effects can be systemic with involvement with several other organ systems. This prospective cohort study from Wuhan, China looked to find an association with COVID-19 infections and development of acute kidney injury (AKI) and establish an association with kidney disease and mortality among patients infected with COVID-19.

Study Design

• 701 patients diagnosed with symptomatic COVID-19 from the Tongji Hospital in China from Jan. 28 to Feb. 11, 2020 were enrolled in the study.

• Medical records of patients were reviewed for clinical symptoms, medications, lab data including blood counts, liver and renal functions, CRP, ESR, procalcitonin, lactate dehydrogenase, and creatine kinase levels.

• Severity of disease was staged, and the number of AKIs in patients was determined.

Results

• Admission labs showed elevated serum creatinine in 14.4% of the patients and elevated blood urea nitrogen (BUN) in 13.1%. eGFR <60ml/min was reported in 13.1% of patients.

• During the patients’ hospitalization, 5.1% developed AKIs, with increased incidence among those with elevated baseline creatinine vs those with normal (11.9% vs 4.0%).

• In-hospital deaths among all patients were at 16.1%, and 33.7% among those with elevated creatinine baseline.

• Cox regression analysis showed that proteinuria, hematuria, elevated creatinine or BUN baseline, peak serum creatinine >133umol/l and AKI greater than stage 2 were associated with an in-hospital death.

• Antivirals, antibiotics and glucocorticoids were the three most common types of medication given to patients. Those with AKIs were more likely treated with antivirals and glucocorticoids.

Significance

• Patients hospitalized for COVID-19 and had kidney disease on admission were more likely to be transferred to ICU and mechanically ventilated, as well as at higher risk for an in-hospital death.

• Renal function in COVID-19 patients should be monitored and any altered function should be treated early in order to prevent worse outcomes.

Computed tomography (CT) examinations have a role in the diagnosis and management in patients with COVID-19. Typical CT findings include bilateral ground-glass opacities, pulmonary consolidation, and prominent distribution in the posterior and peripheral parts of the lungs. Currently, chest radiography remains the first-line imaging test for identifying pneumonia due to feasibility and low cost considerations. However, CT examinations are more sensitive and specific and can identify abnormalities earlier in the lungs when compared to chest radiography. Several studies have provided evidence that suggests chest radiography could be normal in a patient with COVID-19 even after the onset and progression of typical clinical symptoms.

CT Imaging Features of COVID-19

• Among the first 41 COVID-19 patients confirmed in Wuhan, China, 98% of patients had bilateral lung involvement. Patients with more severe cases were more likely to have bilateral, multiple lobular and segmental areas of consolidations, whereas admitted patients with mild cases were more likely to have bilateral ground glass opacities (GGOs) and sub-segemental areas of consolidation.

• Consolidation is considered a sign of disease progression. Younger patients tended to have more GGOs, while older patients tended to show more pulmonary consolidation.

• Notably, lung cavitation, discrete pulmonary nodules, pleural effusion and lymphadenopathy are absent.

• Chung et al. described the crazy-paving pattern often associated with COVID-19 where GGOs with superimposed interlobular and intralobular septal thickening reflect interstitial lesions.

Diagnostic Considerations

• The current nucleic acid test nasopharyngeal/throat swab is the gold standard for the diagnosis of COVID-19. However, some cases have shown that patients may have multiple negative test results or false-negative results but positive chest CT scans.

• Fang et al. compared the sensitivity of initial chest CT and RT-PCR for COVID-19, and the detection rate for initial CT (98%) was higher than that for first RT-PCR (71%) (P<0.001).

• CT features may be useful for the clinical diagnosis of patients with a typical clinical presentation, detailed exposure, travel history, even if nucleic acid test results prove negative.

Summary

CT imaging characteristics of COVID-19 include posterior and peripheral distribution of GGOs and pulmonary consolidation. Analysis of patients with COVID-19 at different stages using CT may provide insight into disease progression and prognosis. CT may be used in the clinical diagnosis of COVID-19, despite negative nucleic acid test results.

Review by Vida Motamedi on 4/4/20.

Introduction

• The COVID-19 pandemic disproportionately affects older adults. Older adults with co-morbidities and/or on certain medications, ACE inhibitors (ACEi) or angiotensin II receptor blockers (ARBs), are at increased risk of infection.

Background

• This review discusses COVID-19 transmission, clinical symptoms, mortality, and possible treatments as they relate to older adults.

Study Design

• Literature review article

Findings

• Older adults are at increased risk of infection due to co-morbidities including hypertension and diabetes

  • In the population of adults over age 60 years, 63.1% have hypertension

  • 38% of adults over age 65 have chronic kidney disease (CKD), and 26.8% have diabetes

  • A proposed viral mechanism involves entry via spike proteins on the SARS-CoV-2 anchoring to the ACE-2 receptor which increases infection risk for patients taking ACEi or ARBs

• Clinical presentation in older adults is similar to the general population whose presenting symptoms are fever (98%), cough (76%), dyspnea (55%), and myalgias or fatigue (44%)

  • In a small study of adults over 70 years, the most common presenting COVID-19 symptoms were dyspnea (76%), fever (52%), and cough (48%)

• 86% of older adults who presented with symptoms had comorbidities including:

  • CKD (48%), congestive heart failure (43%), chronic obstructive pulmonary disease (33%), and diabetes (33%)

• In the majority of COVID-19 cases in older adults, disease course was complicated by organ damage including:

  • ARDS (71%), acute kidney injury (20%), cardiac injury (33%), and liver dysfunction (15%)

  • 67% required management with vasopressor support

• Mortality is greater in older adults, especially aged 85 years and older

  • A recent study of 4,266 cases in the U.S. showed that the case fatality rate was highest in patients aged 85 years and older (10-27%) compared to patients aged 65 to 84 (3-11%) and patients aged 54 years and below (less than 1%)

• Treatment is currently supportive as there is no FDA-approved drugs at the time this review was published

Conclusion

• Older adults often have multi-morbidities and are on medications that contribute to their increased risk of COVID-19 infection

• Among patients with COVID-19, adults aged 65 years and older have increased mortality and it is greatest in those 85 years and older

Taiwan began their response to COVID-19 on the day that China reported to the WHO of pneumonia from unknown causes (12/31/2019). Tawainese officials boarded all planes and assessed patients for pneumonia symptoms before they were allowed to deplane. The Central Epidemic Command Center (CECC) was activated and public effort emerged to counteract the crisis. 124 actions were instituted.

Main actions:

1. Border control of air and sea

2. Identifying cases by Integrating their national insurance database with the Immigration and Customs database (done in under 72 hours)

   • This gave real-time alerts during clinic visits based on patients travel history + symptoms to help identify cases

     • • Person's with low risk: were sent a health declaration border pass via text message. Helped with faster immigration clearance

       • Person with high risk: quarantined at home and were tracked through their phone to ensure they remained at home

3. Proactively seeked out patients with severe respiratory symptoms using their national database

4. Established a toll-free number for citizens to report suspicious symptoms in themselves or others

• As numbers increased, each city established their own hotline

5. Resource allocation:

   • • 4 million masks were released daily - used government funds + military personnel to increase masks production

       1. • By January 20th: stockpile of 44 million surgical masks, 1.9 million N95 masks, and 1100 negative-pressure isolation rooms.

     • Maximum of 3 masks were allowed for purchase

     • Capped the price of masks

6. The president of Taiwan gave daily briefings:

   • • When and where to wear a mask

     • Advised against hoarding masks to prevent healthcare shortage

     • Instructions on proper handwashing and social distancing

     • Provided transparent information on the evolving epidemic

7. Policies were created to assists schools, businesses and furloughed workers

8. Government provided food and frequent health checks to those diagnosed - helped prevent disease stigma.

Taiwan outcomes (as of February 24, 2020):

1. 30 cases of COVID 19.

As of March 27, 2020 Italy was the country second most affected by COVID-19. By March 18, 2020, 17713 people tested positive for SARS-CoV-2 in Lombardy and 1593 (9%) were admitted to the ICU. This is the first large retrospective analysis of patients with COVID-19 in Europe.

Results

• This retrospective review includes 1591 COVID-19 positive patients admitted to the ICU at one of the 72 hospitals in the Lombardy ICU Network between February 20 and March 18, 2020

• Patient characteristics

  • 82% were male

  • Median age was 63 years

  • 23% of patients were 71 years or older and 13% were younger than 51 years

  • 49% had hypertension

  • 21% had cardiovascular disease

  • 18% had hypercholesterolemia

  • 4% had COPD

• The reported proportion of patients requiring any respiratory support and invasive mechanical ventilation were higher than previously reported in other countries

  • 99% of patients admitted to the ICU required respiratory support

  • 88% required endotracheal intubation with mechanical ventilation and 11% received noninvasive ventilation

  • 89% required at least 50% F_IO2 and 12% required 100% F_IO2

  • F_IO2 was higher in older patients (>63 years old) and Pa_O2/F_IO2 was higher in younger patients (<63 years old)

    • Median Pa_O2/F_IO2 was 160 representing severe hypoxia

  • 27% of patients were treated with prone ventilation

  • 1% of patients required ECMO

• ICU mortality was 26%

  • Mortality was significantly lower in younger adults (<63 years old) compared to older adults (15% vs 36%)

  • 58% of patients remained in the ICU at the study endpoint

• Hypertension was more prevalent in patients who died in the ICU (63%) compared to patients who were discharged (40%)

  • Patients with hypertension were significantly older, required higher PEEP levels and had a lower Pa_O2/F_IO2