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2.
Clin Infect Dis ; 2021 Aug 14.
Article in English | MEDLINE | ID: covidwho-1704207

ABSTRACT

BACKGROUND: Follow-up study of Coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge. METHODS AND FINDINGS: A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit. CONCLUSIONS: Physiological, laboratory, radiological or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, liver functions are common in patients who recovered from COVID-19 up to 12months post-discharge.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318906

ABSTRACT

Background: Solid transplant patients are susceptible to Pneumocystis jirovecii pneumonia (PJP). While the vast majority of PJP cases occur within the first 6 months after transplantation, very few PJP cases are seen beyond 1 year post transplantation (late-onset PJP). PJP and coronavirus disease 2019 (COVID-19, caused by infection with SARS-CoV-2) share quite a few common clinical manifestations and imaging findings, making the diagnosis of PJP often underappreciated during the current COVID-19 pandemic. To date, only 1 case of kidney transplantation who developed COVID-19 and late-onset PJP has been reported, but this patient also suffered from many other infections and died from respiratory failure and multiple organ dysfunction syndrome. A successful treatment of kidney patients with COVID-19 and late-onset PJP has not been reported. Case presentation: We present a case of a 55-year-old male kidney transplant patient with COVID-19 who also developed late-onset PJP. He received a combined strategy, including specific anti-pneumocystis therapy, symptomatic supportive therapy, adjusted immunosuppressive therapy, and use of antiviral/antibiotics drugs, ending with a favorable outcome. Conclusions: This case highlights the importance of prompt and differential diagnosis of PJP in kidney transplant patients with SARS-CoV-2 infection. Further studies are required to clarify if kidney transplant patients with COVID-19 could be prone to develop late-onset PJP and how these patients should be treated.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315595

ABSTRACT

Background: Since the first public genome of SARS-CoV-2, over 170,000 genome sequences of the virus have been shared by researchers world-wide (till November 1st 2020). Multiplex PCR targeting SARS-CoV-2 followed by massively parallel sequencing (MPS) and/or nanopore sequencing is a widely used strategy to recover the genome from primary samples. However, the bias of amplification among different amplicons should not be ignored, which might lead to uneven sequencing coverage on the viral genome.MethodsWe aim to develop a novel multiplex PCR panel to achieve an improved coverage evenness of SARS-CoV-2. We adapt long amplicons (~1000-bp) for the panel and thus reduced the number of primer pairs. The panel was validated with clinical samples and sequenced via MPS sequencing systems and a portable nanopore sequencing device MinION. We evaluated the full-genome coverage evenness and its dependence on viral loads of the long amplicon panel;we then compared it with a 98-plex panel provided by the ARTIC network. The accuracy to identify viral genomic variations based on the panel and sequencing with MinION was assessed.ResultsWe developed a two-pool 36-plex panel for full-genome sequencing of SARS-CoV-2, whose amplicon size ranged from 880 to 1027 bp. For samples with a <30 C t value, >90% viral genome could be recovered with a high sequencing depth (>0.2 mean depth) by using the long-amplicon panel (n = 36), compared with 79-88% highly covered genome region for the ARTIC panel (n = 5). The coverage evenness of the long-amplicon panel was also less affected by low viral titers and not dependent on sequencing data amount. With MinION sequencing, the consensus viral genomes could be reliably recovered. However, a high false positive rate was observed to identify sub-clonal genomic variations with a <0.6 frequency.ConclusionA novel multiplex PCR panel for full-genome sequencing of SARS-CoV-2 with improved coverage evenness and low requirement of data throughput was validated with clinical samples. Amplification of SARS-CoV-2 with the panel followed by MinION sequencing could generate reliable consensus genome sequences, but the detection of non-dominating viral populations within host is error-prone.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313360

ABSTRACT

The resurgence of coronavirus disease 2019 (COVID-19) has been seen in many counties where outbreaks appear to be leveling off. While China experienced a dramatic decline of COVID-19 at the outset of 2020, regional outbreaks continuously emerged in recent months. In Guangzhou, a small outbreak emerged in March and April involving less than 100 residents, and a comprehensive and near-real-time genomic surveillance of SARS-CoV-2 was conducted. When confirmed cases among overseas travelers increased, public health authorities enhanced measures as shifting self-quarantine to central quarantine and SARS-CoV-2 testing for all overseas travelers. From 109 imported cases we found diverse viral variants distributing in the global viral phylogeny, which were usually shared within households but not among passengers on the same flight. Nonetheless, local transmission was predominately attributed to two specific variants imported from Africa, including the local cases who reported no direct/indirect contact with imported cases. The introducing events of the virus were identified or deduced before enhanced measures were taken. These results show that the interventions are effective in containing the spread of SARS-CoV-2, and also rule out the possibility of cryptic transmission of viral variants from the first wave in January and February. Moreover, we found that intra-host viral diversity was usually different between close contacts, implying a transmission bottleneck of SARS-CoV-2. Our study provides evidence and emphasizes the importance of controls for oversea travelers in the context of the pandemic, and exemplifies how viral genomic data facilitates COVID-19 surveillance and prevention.Funding: This study was supported by National Natural Science Foundation of China (31870079, 91953122, 31871326), National Science and Technology Major Project of the Ministry of Science and Technology of China (2017ZX10103011, 2018ZX10305410, 2018ZX10201001), Guangdong Provincial Novel Coronavirus Scientific and Technological Project (2020111107001), Guangdong Basic and Applied Basic Research Foundation (2020A1515010776 and 2020B1515020057) and the Beijing Nova Program (Z181100006218114 and Z181100006218110) to M.N. and P.L..Conflict of Interest: The authors declare no competing interests.Ethical Approval: This study was approved by the ethics committee of the Center for Disease Control and Prevention (CDC) of Guangzhou (GZCDC-ECHR-2020P0002). Written informed consent was obtained from patients about the surveillance and data related to disease control and further analysis. All information regarding individual persons has been anonymized in this study.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310719

ABSTRACT

Objective: Lung computed tomography (CT) image was considered as supplementary diagnostic criteria for COVID-19 in the newest diagnosis and treatment program;however, the diagnostic effectiveness of lung CT in patients that have a strict screening for symptoms, history and reverse transcription-polymerase chain reaction (RT-PCR) testing remain unclear. To share our experience about elective surgery during the COVID-19 pandemic and to analyze the effectiveness and necessity of lung CT for screening COVID-19 in elective surgery patients from low risk areas.MethodsBased on the database of our Hospital Information System, participants were all patients receiving elective surgery in departments of general surgery, hepatological surgery, orthopedics, neurosurgery and urology at our hospital from 11 January, 2020 to 11 May, 2020.ResultsIn total, 2375 patients (1150 females and 1225 males) were enrolled in this current study. The mean age was 52 years old, ranging from 6 to 94. All the RT-PCR results of these 2375 patients were negative, including the patients with fever. The most common features on lung CT were nodular lesions (n=624, 26.3%) and striplike lesions (n=467, 19.7%). While, there were only 120 patients (5.1%) with ground-glass opacities (GGO) and 54 patients (2.3%) with lung consolidations on the lung CT, which were ruled out the COVID-19 by the RT-PCR results, clinical manifestation, fever screen, contact history and travel history. During the hospital stay, a total number of 1085 patients were screened with temperature ≥ 37.3℃, which were ruled out COVID-19 by consultation of special fever clinic and respiratory department.ConclusionsAfter strict screening for symptoms, history (contact COVID-19 patients or travelling to high-risk areas) and RT-PCR testing, lung CT image was not recommended as routine examination in patients receiving selective surgery from the low-risk areas of COVID-19.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325219

ABSTRACT

In the middle of March, the World Health Organization declared the outbreak of COVID-19 caused by SARS-CoV-2 infection a global pandemic. While China experienced a dramatic decline in daily growth rate of COVID-19, multiple importations of new cases from other countries and their related local infections caused a rapid rise. Between March 12 and April 15, we collected nasopharyngeal samples from 109 imported cases from 25 countries and 69 local cases in Guangzhou, China. In order to characterize the transmission patterns and genetic evolution of this virus among different populations, we sequenced the genome of SARS-CoV-2. The imported viral strains were assigned to lineages distributed in Europe (33.0%), America (17.4%), Africa (25.7%), or Southeast/West Asia (23.9%). Importantly, 10 imported cases from Africa formed two novel sub-lineages not identified in global tree previously. A detailed analysis showed that the imported viral strains from Philippines and Pakistan were closely related and within the same sub-lineage, whereas Ethiopia had varied lineages in the African phylogenetic tree. In spite of the diversity of imported SARS-CoV-2, 60 of 69 local infections could be traced back to two specific small lineages imported from Africa. A combined genetic and epidemiological analysis revealed a high-resolution transmission network of the imported SARS-CoV-2 in local communities, which might help inform the public health response and genomic surveillance in other cities and regions. Finally, we observed in-frame deletions on seven loci of SARS-CoV-2 genome, some of which were intra-host mutations, and they exhibited no enrichment on the S protein. Our findings provide new insight into the viral phylodynamics of SARS-CoV-2 and beta coronavirus.

8.
Ann Clin Microbiol Antimicrob ; 20(1): 83, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1582061

ABSTRACT

BACKGROUND: Solid transplant patients are susceptible to Pneumocystis jirovecii pneumonia (PJP). While the vast majority of PJP cases occur within the first 6 months after transplantation, very few PJP cases are seen beyond 1 year post-transplantation (late-onset PJP). PJP and coronavirus disease 2019 (COVID-19, caused by infection with SARS-CoV-2) share quite a few common clinical manifestations and imaging findings, making the diagnosis of PJP often underappreciated during the current COVID-19 pandemic. To date, only 1 case of kidney transplantation who developed COVID-19 and late-onset PJP has been reported, but this patient also suffered from many other infections and died from respiratory failure and multiple organ dysfunction syndrome. A successful treatment of kidney patients with COVID-19 and late-onset PJP has not been reported. CASE PRESENTATION: We present a case of a 55-year-old male kidney transplant patient with COVID-19 who also developed late-onset PJP. He received a combined treatment strategy, including specific anti-pneumocystis therapy, symptomatic supportive therapy, adjusted immunosuppressive therapy, and use of antiviral drugs/antibiotics, ending with a favorable outcome. CONCLUSIONS: This case highlights the importance of prompt and differential diagnosis of PJP in kidney transplant patients with SARS-CoV-2 infection. Further studies are required to clarify if kidney transplant patients with COVID-19 could be prone to develop late-onset PJP and how these patients should be treated.


Subject(s)
COVID-19 , Kidney Transplantation , Pneumonia, Pneumocystis , COVID-19/complications , COVID-19/drug therapy , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/drug therapy
9.
J Med Virol ; 94(1): 327-334, 2022 01.
Article in English | MEDLINE | ID: covidwho-1410052

ABSTRACT

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an important role in COVID-19 pandemic control and elimination efforts, especially by elucidating its global transmission network and illustrating its viral evolution. The deployment of multiplex PCR assays that target SARS-CoV-2 followed by either massively parallel or nanopore sequencing is a widely-used strategy to obtain genome sequences from primary samples. However, multiplex PCR-based sequencing carries an inherent bias of sequencing depth among different amplicons, which may cause uneven coverage. Here we developed a two-pool, long-amplicon 36-plex PCR primer panel with ~1000-bp amplicon lengths for full-genome sequencing of SARS-CoV-2. We validated the panel by assessing nasopharyngeal swab samples with a <30 quantitative reverse transcription PCR cycle threshold value and found that ≥90% of viral genomes could be covered with high sequencing depths (≥20% mean depth). In comparison, the widely-used ARTIC panel yielded 79%-88% high-depth genome regions. We estimated that ~5 Mbp nanopore sequencing data may ensure a >95% viral genome coverage with a ≥10-fold depth and may generate reliable genomes at consensus sequence levels. Nanopore sequencing yielded false-positive variations with frequencies of supporting reads <0.8, and the sequencing errors mostly occurred on the 5' or 3' ends of reads. Thus, nanopore sequencing could not elucidate intra-host viral diversity.


Subject(s)
Genome, Viral/genetics , Multiplex Polymerase Chain Reaction/methods , Nanopore Sequencing/methods , SARS-CoV-2/genetics , Whole Genome Sequencing/methods , COVID-19 , High-Throughput Nucleotide Sequencing/methods , Humans , Nasopharynx/virology , RNA, Viral/genetics , Sequence Analysis, RNA/methods
10.
Clin Infect Dis ; 2021 Aug 14.
Article in English | MEDLINE | ID: covidwho-1356658

ABSTRACT

BACKGROUND: Follow-up study of Coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge. METHODS AND FINDINGS: A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit. CONCLUSIONS: Physiological, laboratory, radiological or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, liver functions are common in patients who recovered from COVID-19 up to 12months post-discharge.

11.
J Clin Microbiol ; 59(8): e0007921, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1218187

ABSTRACT

While China experienced a peak and decline in coronavirus disease 2019 (COVID-19) cases at the start of 2020, regional outbreaks continuously emerged in subsequent months. Resurgences of COVID-19 have also been observed in many other countries. In Guangzhou, China, a small outbreak, involving less than 100 residents, emerged in March and April 2020, and comprehensive and near-real-time genomic surveillance of SARS-CoV-2 was conducted. When the numbers of confirmed cases among overseas travelers increased, public health measures were enhanced by shifting from self-quarantine to central quarantine and SARS-CoV-2 testing for all overseas travelers. In an analysis of 109 imported cases, we found diverse viral variants distributed in the global viral phylogeny, which were frequently shared within households but not among passengers on the same flight. In contrast to the viral diversity of imported cases, local transmission was predominately attributed to two specific variants imported from Africa, including local cases that reported no direct or indirect contact with imported cases. The introduction events of the virus were identified or deduced before the enhanced measures were taken. These results show the interventions were effective in containing the spread of SARS-CoV-2, and they rule out the possibility of cryptic transmission of viral variants from the first wave in January and February 2020. Our study provides evidence and emphasizes the importance of controls for overseas travelers in the context of the pandemic and exemplifies how viral genomic data can facilitate COVID-19 surveillance and inform public health mitigation strategies.


Subject(s)
COVID-19 , SARS-CoV-2 , Africa , COVID-19 Testing , China/epidemiology , Genomics , Humans
12.
J Med Virol ; 92(11): 2600-2606, 2020 11.
Article in English | MEDLINE | ID: covidwho-935122

ABSTRACT

To investigate the inflammatory factors and lymphocyte subsets which play an important role in the course of severe coronavirus disease 2019 (COVID-19). A total of 27 patients with severe COVID-19 who were admitted to Tongji Hospital in Wuhan from 1 to 21 February 2020 were recruited to the study. The characteristics of interleukin-1ß (IL-1ß), IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF)-α, C-reactive protein (CRP), serum ferritin and procalcitonin (PCT), and lymphocyte subsets of these patients were retrospectively compared before and after treatment. Before treatment, there was no significant difference in most inflammatory factors (IL-1ß, IL-2R, IL-6, IL-8, IL-10, CRP, and serum ferritin) between male and female patients. Levels of IL-2R, IL-6, TNF-α, and CRP decreased significantly after treatment, followed by IL-8, IL-10, and PCT. Serum ferritin was increased in all patients before treatment but did not decrease significantly after treatment. IL-1ß was normal in most patients before treatment. Lymphopenia was common among these patients with severe COVID-19. Analysis of lymphocyte subsets showed that CD4+ and particularly CD8+ T lymphocytes increased significantly after treatment. However, B lymphocytes and natural killer cells showed no significant changes after treatment. A pro-inflammatory response and decreased level of T lymphocytes were associated with severe COVID-19.


Subject(s)
COVID-19/immunology , Inflammation/immunology , Lymphocyte Subsets/immunology , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/therapy , China , Cytokines/blood , Cytokines/immunology , Female , Humans , Interleukins/blood , Lymphocyte Count , Male , Middle Aged , Prognosis , Retrospective Studies , Severity of Illness Index
13.
Hepatol Int ; 14(5): 723-732, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-834069

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a major international public health concern. This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury. METHODS: A fraction of 657 COVID-19 patients were retrospectively analyzed. Clinical and laboratory data were derived from electronic medical records and compared between patients with or without liver injury. Multivariate logistic regression method was used to analyze the risk factors for liver injury. RESULTS: Among 657 patients, 303 (46.1%) patients had liver injury with higher rate in severe/critically ill patients [148/257 (57.6%)] than those in moderate cases [155/400 (38.8%)]. The incidence of liver injury was much higher in male [192/303 (63.4%)] than female [111/303 (36.6%)], and in severe/critical patients [148/303 (48.8%)] with percutaneous oxygen saturation ≤ 93% [89/279 (31.9%)] or peak body temperature ≥ 38.5 °C [185/301 (61.5%)] on admission. Liver injury-related inflammations included increased white blood cells, neutrophils and decreased lymphocytes. More patients with liver injury than without had increased serum IL-2R, TNFα, ferritin, hsCRP, PCT, ESR, γ-GT, and LDH. Multivariate regression analysis revealed that increasing odds of liver injury were related to male, higher serum hsCRP (≥ 10 mg/L), and neutrophil-to-lymphocyte ratio (NLR) (≥ 5). Moreover, more deceased patients (14/82 (17%)) had significantly elevated serum TBIL than discharged patients [25/532 (4.7%)]. CONCLUSION: Liver injury is a common complication in COVID-19 patients. The potential risk factors of liver injury include male, hsCRP and NLR score. A close monitor of liver function should be warned in COVID-19 patients, especially in severe/critical individuals.


Subject(s)
Coronavirus Infections , Cytokines/blood , Hepatic Insufficiency , Leukocyte Count/methods , Liver Function Tests , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Female , Hepatic Insufficiency/blood , Hepatic Insufficiency/epidemiology , Hepatic Insufficiency/virology , Humans , Incidence , Liver Function Tests/methods , Liver Function Tests/statistics & numerical data , Male , Middle Aged , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Retrospective Studies , Risk Factors , SARS-CoV-2 , Sex Factors
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