Nervous system involvement after infection with COVID-19 and other coronaviruses.

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.

Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease.

The emergence of SARS-CoV-2 has created an international health crisis, and small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection owing to low-affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here, we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promoter (K18). In contrast to nontransgenic mice, intranasal exposure of K18-hACE2 animals to 2 different doses of SARS-CoV-2 resulted in acute disease, including weight loss, lung injury, brain infection, and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals showed increases in transcripts involved in lung injury and inflammatory cytokines. In the low-dose challenge groups, there was a survival advantage in the female mice, with 60% surviving infection, whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared with female mice. To our knowledge, this is the first highly lethal murine infection model for SARS-CoV-2 and should be valuable for the study of SARS-CoV-2 pathogenesis and for the assessment of MCMs.

A prospective evaluation of lung function at three and six months in patients with previous SARS-COV-2 pneumonia.

OBJECTIVE: This study investigated the consequences of Coronavirus Disease 2019 (COVID-19) pneumonia on lung function in the first 6 months after hospital discharge. METHODS: A prospective lung function assessment in SARS-CoV2 patients with COVID-19 pneumonia, hospitalized between March and April 2020, was conducted with spirometry measurements including lung volumes, mainly total lung capacity (TLC), lung diffusion capacity for carbon monoxide (DLCO) collected at 3 months after hospital discharge. Patients with restrictive ventilatory defect or impaired DLCO or both were re-evaluated at 6 months with global spirometry and chest HRCT scan. RESULTS: Among 40 consecutive patients, 19 (48%) had normal pulmonary functional tests (group A), and 21 (52%) showed residual lung function abnormalities at 3 months after hospital discharge (group B). In group B, 4 patients (19%) had only loss of lung volume as shown by TLC reduction (group 1), 13 patients (62%) had decreased both TLC and DLCO (group 2), and 4 patients (19%) had isolated reduction in DLCO (group 3). At 6-month follow-up in group 1, although all patients improved, only one normalized total lung capacity (TLC). In group 2, TLC and DLCO increased significantly (p < 0.01), but only 3 patients reached normal values. In group 3, DLCO improved for most patients, normalizing in 50% of them. At 6-months significant correlations between an internal-built chest HRCT scan severity score and TLC (r2 = 0.33; p < 0.01) and DLCO (r2 = 0.32; p < 0.01) were found. CONCLUSIONS: Nearly 50% of patients recovered in the post-critical phase. Most of those with abnormal pulmonary function tests at 3 months improved subsequently, but only another 29% (6 out of 21) reached normal values at 6 months. These results indicate that lung function spontaneous recovery is faster at first and occurs more slowly thereafter, leaving more than one third (15 out of 40) of patients with abnormal lung function tests at 6 months.

Clinical features of COVID-19 and SARS epidemics. A literature review.

SARS-CoV-2, responsible for the current pandemic, is a novel strain of the Coronaviridae family, which has infected humans as a result of the leap to a new species. It causes an atypical pneumonia similar to that caused by SARS-CoV in 2003. SARS-CoV-2 has currently infected more than 9,200,000 people and caused almost 480,000 deaths worldwide. Although SARS-CoV-2 and SARS-CoV have similar phylogenetic and pathogenetic characteristics, they show important differences in clinical manifestations. We have reviewed the recent literature comparing the characteristics of the two epidemics and highlight their peculiar aspects. An analysis of all signs and symptoms of 3,365 SARS patients and 23,280 COVID-19 patients as well as of the comorbidities has been carried out. A total of 17 and 75 studies regarding patients with SARS and COVID-19, respectively, were included in the analysis. The analysis revealed an overlap of some symptoms between the two infections. Unlike SARS patients, COVID-19 patients have developed respiratory, neurological and gastrointestinal symptoms, and, in a limited number of subjects, symptoms involving organs such as skin and subcutaneous tissue, kidneys, cardiovascular system, liver and eyes. This analysis was conducted in order to direct towards an early identification of the infection, a suitable diagnostic procedure and the adoption of appropriate containment measures.

SARS-CoV 2 Infection (Covid-19) and Cardiovascular Disease in Africa: Health Care and Socio-Economic Implications.

The current pandemic of SARS-COV 2 infection (Covid-19) is challenging health systems and communities worldwide. At the individual level, the main biological system involved in Covid-19 is the respiratory system. Respiratory complications range from mild flu-like illness symptoms to a fatal respiratory distress syndrome or a severe and fulminant pneumonia. Critically, the presence of a pre-existing cardiovascular disease or its risk factors, such as hypertension or type II diabetes mellitus, increases the chance of having severe complications (including death) if infected by the virus. In addition, the infection can worsen an existing cardiovascular disease or precipitate new ones. This paper presents a contemporary review of cardiovascular complications of Covid-19. It also specifically examines the impact of the disease on those already vulnerable and on the poorly resourced health systems of Africa as well as the potential broader consequences on the socio-economic health of this region.

Comparison of acute pneumonia caused by SARS-COV-2 and other respiratory viruses in children: a retrospective multi-center cohort study during COVID-19 outbreak.

BACKGROUND: Until January 18, 2021, coronavirus disease-2019 (COVID-19) has infected more than 93 million individuals and has caused a certain degree of panic. Viral pneumonia caused by common viruses such as respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses have been more common in children. However, the incidence of COVID-19 in children was significantly lower than that in adults. The purpose of this study was to describe the clinical manifestations, treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak. METHODS: Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study. A total of 64 children with COVID-19 were defined as the COVID-19 cohort, of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort. Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort. The epidemiologic, clinical, and laboratory findings were compared by Kolmogorov-Smirnov test, t-test, Mann-Whitney U test and Contingency table method. Drug usage, immunotherapy, blood transfusion, and need for oxygen support were collected as the treatment indexes. Mortality, intensive care needs and symptomatic duration were collected as the outcome indicators. RESULTS: Compared with the viral pneumonia cohort, children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19 (53/64 vs. 23/284), were of older median age (6.3 vs. 3.2 years), and had a higher proportion of ground-glass opacity (GGO) on computed tomography (18/40 vs. 0/38, P < 0.001). Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases (1/40 vs. 38/284, P = 0.048), and lower cases with high fever (3/40 vs. 167/284, P < 0.001), requiring intensive care (1/40 vs. 32/284, P < 0.047) and with shorter symptomatic duration (median 5 vs. 8 d, P < 0.001). The proportion of cases with evaluated inflammatory indicators, biochemical indicators related to organ or tissue damage, D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort (P < 0.05). No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs (lopinavir-ritonavir, ribavirin, and arbidol) as compared with duration in 39 children without antiviral therapy [median 10 vs. 9 d, P = 0.885]. CONCLUSION: The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia. Lopinavir-ritonavir, ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19. During the COVID-19 outbreak, attention also must be given to children with infection by other pathogens infection.

[Coagulopathy and thrombosis: similarities and differences among pathogenic coronaviruses].

One of the most significant negative prognostic factors in patients suffering from the disease caused by SARS-CoV-2 (COVID-19) is the development of coagulopathy, associated with abnormal laboratory findings, such as increased D-dimer, and venous thromboembolic complications, requiring thromboprophylactic strategies. The main clinical characteristics of COVID-19 patients are revised here as compared to other coronavirus infections, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), emphasizing clinical, diagnostic and therapeutic aspects.

Clinical Symptom Differences Between Mild and Severe COVID-19 Patients in China: A Meta-Analysis.

Objective: The prognosis of mild and severe patients has prominent differences during the prevalence of COVID-19, and it will be significant to identify patients' potential risk of progressing to severe cases according to their first clinical presentations. Therefore, we aim to review the clinical symptoms of the COVID-19 epidemic systematically. Methods:We searched PubMed, Embase, Web of Science, and CNKI (Chinese Database) for studies about the clinical features of COVID-19 in China from March 18 to April 18. Then we used REVMAN to conduct a meta-analysis. Results: After screening, 20 articles including 3,326 COVID-19 confirmed cases were selected from 142 articles we retrieved at the beginning of our research. We divided all the cases into a severe group (including severe and critically severe patients) and a mild group according to the "Diagnosis and Treatment Protocol for Novel Coronavirus Infection-Induced Pneumonia" version 4 (trial). Of all the initial symptoms (including fever, cough, abdominal pain, anorexia, chest tightness, diarrhea, dyspnea, expectoration, fatigue, headache, hemoptysis, myalgia, nausea or vomiting, and pharyngalgia) we studied, we found that cough (odds ratio [OR] = 1.4, 95% confidence interval [CI]: 1.2-1.7; p < 0.001), fever (OR = 1.5, 95% CI: 1.2-1.9; p < 0.001), dyspnea (OR = 6.2, 95% CI: 3.6-10.6; p < 0.001), diarrhea (OR = 2.6, 95% CI: 1.3-4.9; p < 0.001), fatigue (OR = 2.1, 95% CI: 1.3-3.3; p < 0.01), expectoration (OR = 1.7, 95% CI: 1.2-2.6; p < 0.01), myalgia (OR = 1.6, 95% CI: 0.8-3.1; p < 0.001), hemoptysis (OR = 4.0, 95% CI: 1.5-11.3; p < 0.001), abdominal pain (OR = 7.5, 95% CI: 2.4-23.4; p < 0.001), and anorexia (OR = 2.8, 95% CI: 1.5-5.1; p < 0.001) had a different distribution in two groups and were statistically significant (p < 0.05). Conclusion:COVID-19 patients whose initial manifestation is dyspnea, hemoptysis, anorexia, diarrhea, or fatigue, especially abdominal pain should be closely monitored to prevent disease deterioration.

Immunopathogenesis of Coronavirus-Induced Acute Respiratory Distress Syndrome (ARDS): Potential Infection-Associated Hemophagocytic Lymphohistiocytosis.

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, introduced the third highly pathogenic coronavirus into humans in the 21st century. Scientific advance after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic and Middle East respiratory syndrome coronavirus (MERS-CoV) emergence enabled clinicians to understand the epidemiology and pathophysiology of SARS-CoV-2. In this review, we summarize and discuss the epidemiology, clinical features, and virology of and host immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2 and the pathogenesis of coronavirus-induced acute respiratory distress syndrome (ARDS). We especially highlight that highly pathogenic coronaviruses might cause infection-associated hemophagocytic lymphohistiocytosis, which is involved in the immunopathogenesis of human coronavirus-induced ARDS, and also discuss the potential implication of hemophagocytic lymphohistiocytosis therapeutics for combating severe coronavirus infection.

A Comprehensive Review of Animal Models for Coronaviruses: SARS-CoV-2, SARS-CoV, and MERS-CoV.

The recent outbreak of coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.

Coronavirus-associated kidney outcomes in COVID-19, SARS, and MERS: a meta-analysis and systematic review.

OBJECTIVES: A meta-analysis and systematic review was conducted on kidney-related outcomes of three recent pandemics: SARS, MERS, and COVID-19, which were associated with potentially fatal acute respiratory distress syndrome (ARDS). METHODS: A search of all published studies until 16 June 2020 was performed. The incidence/prevalence and mortality risk of acute and chronic renal events were evaluated, virus prevalence, and mortality in preexisting hemodialysis patients was investigated. RESULTS: A total of 58 eligible studies involving 13452 hospitalized patients with three types of coronavirus infection were included. The reported incidence of new-onset acute kidney injury (AKI) was 12.5% (95% CI: 7.6%-18.3%). AKI significantly increased the mortality risk (OR = 5.75, 95% CI 3.75-8.77, p < 0.00001) in patients with coronavirus infection. The overall rate of urgent-start kidney replacement therapy (urgent-start KRT) use was 8.9% (95% CI: 5.0%-13.8%) and those who received urgent-start KRT had a higher risk of mortality (OR = 3.43, 95% CI 2.02-5.85, p < 0.00001). Patients with known chronic kidney disease (CKD) had a higher mortality than those without CKD (OR = 1.97, 95% CI 1.56-2.49, p < 0.00001). The incidence of coronavirus infection was 7.7% (95% CI: 4.9%-11.1%) in prevalent hemodialysis patients with an overall mortality rate of 26.2% (95% CI: 20.6%-32.6%). CONCLUSIONS: Primary kidney involvement is common with coronavirus infection and is associated with significantly increased mortality. The recognition of AKI, CKD, and urgent-start KRT as major risk factors for mortality in coronavirus-infected patients are important steps in reducing future mortality and long-term morbidity in hospitalized patients with coronavirus infection.

Characteristics of recovered COVID-19 patients with recurrent positive RT-PCR findings in Wuhan, China: a retrospective study.

BACKGROUND: Two months after the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, tens of thousands of hospitalized patients had recovered, and little is known about the follow-up of the recovered patients. METHODS: The clinical characteristics, reverse transcriptase-polymerase chain reaction (RT-PCR) results from throat swab specimens and the results of serological COVID-19 rapid diagnostic test (RDT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were retrospectively reviewed for a total of 758 recovered patients who were previously hospitalized in 17 hospitals and quarantined at 32 rehabilitation stations in Wuhan, China. RESULTS: In total, 59 patients (7.78%) had recurrent positive findings for COVID-19 on RT-PCR from throat swabs. With regard to antibody detection, 50/59 (84.75%) and 4/59 (6.78%) patients had positive IgG or dual positive IgG/IgM RDT results, respectively. CONCLUSIONS: Some patients who had been quarantined and had subsequently recovered from COVID-19 had recurrent positive RT-PCR results for SARS-CoV-2, and the possibility of transmission of the virus by recovered patients needs further investigation. TRIAL REGISTRATION: Current Controlled Trials ChiCTR2000033580 , Jun 6th 2020. Retrospectively registered.

The major genetic risk factor for severe COVID-19 is inherited from Neanderthals.

A recent genetic association study1 identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative)2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization. Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.

Tuberculosis and COVID-19: Lessons from the Past Viral Outbreaks and Possible Future Outcomes.

Background: The threat of contagious infectious diseases is constantly evolving as demographic explosion, travel globalization, and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results: The PubMed electronic database was systematically searched for relevant articles linking TB, influenza, and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (focusing on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from past outbreaks (other coronaviruses) and influenza pandemic/seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions: Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their lethal synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead. The trial is registered with NCT04327206, NCT01829490, and NCT04121494.

ACE2: Its potential role and regulation in severe acute respiratory syndrome and COVID-19.

COVID-19, a new disease caused by the 2019-novel coronavirus (SARS-CoV-2), has swept the world and challenged its culture, economy, and health infrastructure. Forced emergence to find an effective vaccine to immunize people has led scientists to design and examine vaccine candidates all over the world. Until a vaccine is developed, however, effective treatment is needed to combat this virus, which is resistant to all conventional antiviral drugs. Accordingly, more about the structure, entry mechanism, and pathogenesis of COVID-19 is required. Angiotensin-converting enzyme 2 (ACE2) is the gateway to SARS-CoV and SARS-CoV-2, so our knowledge of SARS-CoV-2 can help us to complete its mechanism of interaction with ACE2 and virus endocytosis, which can be interrupted by neutralizing small molecules or proteins. ACE2 also plays a crucial role in lung injury.

Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19.

OBJECTIVE: To determine the prevalence of D-dimer elevation in coronavirus disease 2019 (COVID-19) hospitalization, trajectory of D-dimer levels during hospitalization, and its association with clinical outcomes. Approach and Results: Consecutive adults admitted to a large New York City hospital system with a positive polymerase chain reaction test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) between March 1, 2020 and April 8, 2020 were identified. Elevated D-dimer was defined by the laboratory-specific upper limit of normal (>230 ng/mL). Outcomes included critical illness (intensive care, mechanical ventilation, discharge to hospice, or death), thrombotic events, acute kidney injury, and death during admission. Among 2377 adults hospitalized with COVID-19 and ≥1 D-dimer measurement, 1823 (76%) had elevated D-dimer at presentation. Patients with elevated presenting baseline D-dimer were more likely than those with normal D-dimer to have critical illness (43.9% versus 18.5%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), any thrombotic event (19.4% versus 10.2%; adjusted odds ratio, 1.9 [95% CI, 1.4-2.6]; P<0.001), acute kidney injury (42.4% versus 19.0%; adjusted odds ratio, 2.4 [95% CI, 1.9-3.1]; P<0.001), and death (29.9% versus 10.8%; adjusted odds ratio, 2.1 [95% CI, 1.6-2.9]; P<0.001). Rates of adverse events increased with the magnitude of D-dimer elevation; individuals with presenting D-dimer >2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). CONCLUSIONS: Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

Lung ultrasonography in patients with COVID-19: comparison with CT.

AIM: To determine whether findings from lung ultrasound and chest high-resolution computed tomography (HRCT) correlate when evaluating COVID-19 pulmonary involvement. MATERIALS AND METHODS: The present prospective single-centre study included consecutive symptomatic patients with reverse transcription polymerase chain reaction (RT-PCR)-proven COVID-19 who were not in the intensive care unit. All patients were assessed using HRCT and ultrasound of the lungs by distinct operators blinded to each other's findings. The number of areas (0-12) with B-lines and/or consolidations was evaluated using ultrasound and compared to the percentage and classification (absent or limited, <10%; moderate, 10-25%; extensive, 25-50%; severe, 50-75%; critical, >75%) of lung involvement on chest HRCT. RESULTS: Data were analysed for 21 patients with COVID-19 (median [range] age 65 [37-90] years, 76% male) and excellent correlation was found between the ultrasound score for B-lines and the classification (p<0.01) and percentage of lung involvement on chest HRCT (r=0.935, p<0.001). In addition, the ultrasound score correlated positively with supplemental oxygen therapy (r=0.45, p=0.041) and negatively with minimal oxygen saturation at ambient air (r=-0.652, p<0.01). CONCLUSION: The present study suggests that among COVID-19 patients, lung ultrasound and HRCT findings agree in quantifying lung involvement and oxygen parameters. In the context of the COVID-19 pandemic, lung ultrasound could be a relevant alternative to chest HRCT.

Chest CT findings in asymptomatic cases with COVID-19: a systematic review and meta-analysis.

AIM: To determine the overall rate of chest imaging findings in asymptomatic cases, describe the most common patterns found, and determine the rate of later symptom development in these initially asymptomatic cases. MATERIALS AND METHODS: The PubMed and EMBASE databases were searched until 1 May 2020, for studies examining the proportion of positive chest imaging findings in asymptomatic cases diagnosed with COVID-19 and a random-effects meta-analysis of proportions was performed. Heterogeneity was assessed using the I2 statistic. RESULTS: Among 858 non-duplicate studies, seven studies with a total of 231 asymptomatic cases met the inclusion criteria. In the primary analysis, the pooled estimate of the overall rate of positive chest computed tomography (CT) findings among asymptomatic cases was 63% (95% confidence interval [CI]: 44-78%). Among 155/231 cases that were followed up for later symptom development, 90/155 remained asymptomatic and 65/155 developed symptoms during the study period (that ranged between seven and 30 days of follow-up). The pooled estimate of the rate of positive chest CT findings was 62% (95% CI: 38-81%) in cases that remained asymptomatic, while it was 90% (95% CI: 49-99%) in cases that developed symptoms. Among CT findings, the pooled estimate of the overall rate of ground-glass opacities (GGO) at CT alone was 71% (95% CI: 50-86%). Among other CT findings reported, 22/231 patients had GGO with consolidation, 7/231 patients had stripe shadows with or without GGO, and 8/231 patients had GGO with interlobular septal thickening. Among initially asymptomatic cases with positive CT findings, the pooled estimate of the overall rate of later symptom development was 26% (95% CI: 14-43%). CONCLUSION: In COVID-19, asymptomatic cases can have positive chest CT findings, and COVID-19 should be considered among cases with CT abnormalities even when there are no other symptoms. There is a need for close clinical monitoring of asymptomatic cases with radiographic findings as a significant percentage will develop symptoms.

COVID-19 Guide for the Rehabilitation Clinician: A Review of Nonpulmonary Manifestations and Complications.

Severe acute respiratory syndrome coronavirus 2-also known as COVID-19-is primarily known for respiratory illness. Although it is clear that patients with moderate to severe cases of COVID-19 will require pulmonary rehabilitation, physiatrists will need to consider effective management plans for COVID-19 survivors with extrapulmonary involvement. This report will summarize key nonpulmonary considerations to guide rehabilitation clinicians who may be involved in the care of COVID-19 survivors with the best available early evidence.