205 Sars-cov-2 reinfection in pregnancy – A case report
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Globally, as of mid August 2021 there have been more than 200 million confirmed cases of COVID-19 reported to WHO. About 80% of COVID-19 cases are asymptomatic and mild, and most of the cases resolved within 2-4 weeks. While severe pneumonia and critical multi-organ failure occurs in 15% and 5% respectively, and can last for 3-6 weeks. The post-COVID symptoms, initially referred to as ‘long COVID’ or ‘long-haul COVID’, are now collectively referred to as ‘post-acute sequelae of SARS-CoV-2 infection” (PASC).
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During these months in which the COVID-19 emergency is waning, the activity of dermatologists has changed substantially. Since the beginning of March 2020, in the Dermatology Clinic at the University Hospital in Turin (Italy), the outpatient access has been significantly reduced and telemedicine has been useful whenever possible, by putting the patient in contact directly with dermatologists or mediated by the general practitioners. However, what we noticed about the local population attending the clinic and through consultations in telemedicine in the months of March and April 2020 was a substantial and unexpected appearance of chilblain-like lesions, in asymptomatic or paucisymptomatic patients (mild fever, cold and asthenia), sometimes belonging to the same family. We underline the fact that none of the observed cases has undergone swab or serological tests, as the skin manifestations so far do not represent sufficient criteria to suspect an underlying coronavirus infection. Despite this fact, those lesions have been described in molecular diagnosed COVID-19 patients and the skin lesions alone were not an enough criteria to submit patient to molecular test. Specifically, we have observed erythematous-oedematous lesions, some with purpuric aspects, located at the fingers, toes and heels, with an acrocyanotic aspect (Figs 1 and 2).1 Idiopathic pernio is an abnormal inflammatory response to cold, damp and non-freezing conditions, typically affecting children, women and the elderly when the first wet colds of autumn and winter occur.2 The precise pathogenesis is unknown, but the condition is thought to represent an abnormal inflammatory response to vascular ischaemia caused by prolonged vasoconstriction in the setting of extended cold exposure.3 Several elements of the comparison between our cases and idiopathic pernio surprised us. First, the high incidence in an unusual season, since perniosis normally occurs more frequently with low temperatures and humidity, and the last two months in northern Italy have been particularly warm and sunny. Another element of interest refers to age, as many paediatric cases have been brought to our attention, as well as men of intermediate and advanced age, rarely affected by the aforementioned pathology. We excluded other possible skin diseases that normally must be placed in differential diagnosis with idiopathic pernio, such as chilblain lupus, connective tissue diseases, Raynaud phenomenon, septic or cholesterol emboli during early stages.4 Pernio has a non-specific histology consisting of dermal oedema plus a superficial and deep monomourfous infiltrate of lymphocytes a histiocytes infiltrate with a specific predisposition for peri-eccrine glands. Necrotic keratinocytes and lymphocytic vasculitis have been noted.5 Nevertheless, we did not have the opportunity to perform biopsy specimens in none of the cases observed, for logistical issues and for avoiding the contagiouness spreading when asking the patients to come to hospital. In conclusion, we deduce that the manifestations observed, in consideration of their high incidence, in an otherwise unusual period, and towards a typically uninvolved population, could justifiably be considered an expression of coronavirus infection in asymptomatic or paucisymptomatic patients. Probably, the serologic test will be able to confirm our suspiciousness. The patients in this manuscript have given written informed consent to the publication of their case details. All authors have nothing to disclose. None.
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Fetal fibronectin
Premature birth
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This study describes possible transmission of novel coronavirus disease 2019 (COVID-19) from an asymptomatic Wuhan resident to 5 family members in Anyang, a Chinese city in the neighboring province of Hubei.
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In a single day, six of 150 (4%) asymptomatic visitors were diagnosed with COVID-19 at a hospital with a universal masking policy. Two inpatients (contacts) subsequently developed symptoms. More rigorous protective measures during visitation periods may need to be included in infection control practices to reduce nosocomial transmissions.
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2019-20 coronavirus outbreak
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Coronavirus Disease 2019 (COVID-19) symptoms are highly various in each patient. CXR are routinely used to monitor the disease progression. However, it is not known whether chest X-Ray (CXR) is a good modality to assess COVID-19 pneumonia.Male, 55 years-old, with pneumonia caused by COVID-19. Discordance was found between patient's clinical status and CXR lesion. On the 7th day of symptoms, patient was clinically well despite severe lesion shown on CXR. On the following day, patient clinically deteriorated despite the improvement on CXR lesion.Improvement of CXR does not always correlate well with patient's clinical status. Clinician have to be careful when using CXR to monitor patient with COVID-19 pneumonia.
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Asymptomatic cases of COVID-19 are a potential source of substantial spread within the community setting.1Kronbichler A Kresse D Yoon S Lee KH Effenberger M Shin JI Asymptomatic patients as a source of COVID-19 infections: a systematic review and meta-analysis.Int J of Inf Dis. 2020; 98: 180-186Summary Full Text Full Text PDF PubMed Scopus (265) Google Scholar However, little information is available about the infectivity and epidemiological significance of people with asymptomatic COVID-19.2Gao M Yang L Chen X et al.A study on infectivity of asymptomatic SARS-CoV-2 carriers.Respiratory Medicine. 2020; 169: 1-5Summary Full Text Full Text PDF Scopus (99) Google Scholar Singapore's testing strategy for severe acute respiratory syndrome coronavirus 2 is designed to detect infection in both symptomatic and asymptomatic people. Various methods are used. Workers in specific industries, such as construction, marine, and process industries, are routinely tested once per week or every two weeks, and all close contacts of those who test positive for COVID-19 are tested as well. All COVID-19 case detection, regardless of symptom status, triggers public health actions, including contact tracing and the quarantining of close contacts. A close contact generally refers to a person who was within 2 m of the index case for at least 30 min (or for shorter durations in high-risk settings).3Yong SEF Anderson DE Wei WE et al.Connecting clusters of COVID-19: an epidemiological and serological investigation.Lancet. 2020; 20: 809-815Summary Full Text Full Text PDF Scopus (177) Google Scholar All quarantined people are tested by PCR at the end of their quarantine period, and are only released from quarantine when they test negative for COVID-19. Serology tests are also done in most people who are infected, to determine the possible duration of their COVID-19 infection, and to assist with epidemiological investigations and containment efforts.3Yong SEF Anderson DE Wei WE et al.Connecting clusters of COVID-19: an epidemiological and serological investigation.Lancet. 2020; 20: 809-815Summary Full Text Full Text PDF Scopus (177) Google Scholar As COVID-19 viral load is typically higher before seroconversion than after, seronegative cases are thought to be more infectious than seropositive cases.4Peeling RW Weddenburn CJ Garcia PJ et al.Serology testing in the COVID-19 pandemic response.Lancet. 2020; 20: e245-e249Summary Full Text Full Text PDF Scopus (226) Google Scholar, 5Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infec Dis 71: 2027–34.Google Scholar To identify the relative infectivity of people with COVID-19 on the basis of their symptom and serology status, we studied all people who completed their quarantine between Aug 1 and Oct 11, 2020, as a result of being close community contacts of people who were infected and who had also undergone serology tests as part of their COVID-19 status assessment. Close contacts who lived in migrant worker dormitories were excluded from this analysis because their living environments were contextually different from community close contacts and because there were separate challenges in identifying cases and their close contacts within the dormitories. Negative binomial regression was done using Python version 3.7.1 (Python Software Foundation, Wilmington, DE, USA) to calculate the incidence rate ratios of a quarantined person from the community testing positive for COVID-19, adjusting for the symptom and serology status of the index case; two-tailed statistical significance was set at 0·05. 628 people with COVID-19 were included in this analysis (appendix). 3790 people were close contacts of an index case and were quarantined. On average, 6·0 people from the community were quarantined per index case. Overall, 89 (2%) of 3790 close community contacts developed COVID-19 while in quarantine. Of these, 50 (56%) of 89 contacts were quarantined because of an asymptomatic index case, whereas 39 (44%) contacts were quarantined because of a symptomatic case.43 (48%) contacts were quarantined because of a seronegative index case, whereas 46 (52%) were quarantined because of a seropositive index case. Negative binomial regression revealed that when adjusted for age, gender, and serology of index case, the incidence of COVID-19 among close contacts of a symptomatic index case was 3·85 times higher than for close contacts of an asymptomatic index case (95% CI2·06–7·19; p<0·0001; appendix). Our findings suggest that people with asymptomatic COVID-19 are infectious but might be less infectious than symptomatic cases. We also identified that the proportion of close contacts who became infected did not depend on the serology status of the index case. One reason for this observation could be that close contacts tend to live or work with the index case and are exposed because of their regular contact with a person who was infectious before turning seropositive. The main limitation of this analysis is that cycle threshold values and viable shedding data were not available for all individuals included. Future studies should explore the relationship between viral loads, viable shedding, and transmission. Nevertheless, these findings suggest that where resources permit, contact tracing should proactively seek people with asymptomatic COVID-19 because they can transmit disease and will need to be contained if a national policy objective is to minimise cases and transmission. However, if resources are limited, then focusing contact tracing around symptomatic people who are easy to identify (by way of them seeking health care) might be more resource-effective in reducing transmission at the population level. We declare no competing interests. Download .pdf (.16 MB) Help with pdf files Supplementary appendix
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By March 8, 2020, 85 cases of coronavirus disease 2019 (COVID-19) had been diagnosed in Denmark and by mid-March an estimated 50% of imported cases were derived from Austria ((SSI, 2020SSI COVID-19 in Denmark, an epidemiological surveillance report, March 12, 2020.2020https://files.ssi.dk/COVID19-overvaagningsrapport-12032020Google Scholar) https://files.ssi.dk/COVID19-overvaagningsrapport-12032020; Correa-Martínez et al., 2020Correa-Martínez C.L. Kampmeier S. Kümpers P. Schwierzeck V. Hennies M. Hafezi W. et al.A pandemic in times of global tourism: super spreading and exportation of COVID-19 cases from a ski area in Austria.J Clin Microbiol. 2020; 58 (e00588-20)PubMed Google Scholar). Between March 3 and March 8, a 49-year-old man went skiing in Ischgl, Austria accompanied by 11 male friends. A few days after returning to Denmark, six travel companions developed symptoms of COVID-19 and tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive. In accordance with the Danish guidelines at that time, none of the six asymptomatic individuals was tested. However, one of these, the 49-year-old man, arranged a self-imposed 2-week home quarantine along with his family of four on March 11. Approximately 1 week later, his wife and 18-year-old daughter developed influenza-like symptoms. The following week, the 15-year-old daughter developed ageusia, while the 8-year-old old daughter presented her usual recurrent cough. The extension of national COVID-19 testing on April 1 led the family to the local test center, where the index person and the daughter presenting ageusia tested SARS-CoV-2 PCR-positive. The wife and two other daughters tested negative. The three negative specimens together with 197 SARS-CoV-2-negative samples from other patients were retested at an external laboratory. All samples remained negative; but the specimens from the wife and youngest daughter were found to be weakly positive. Their initial PCR curves were reassessed and found equally irregular with Ct values of 32 and 35. Three weeks later, all five displayed a serological SARS-CoV-2 N/S IgG response. The asymptomatic index person and the youngest daughter presented the highest IgG titers (chemiluminescence immunoassay (CLIA), iFlash 1800 Shenzhen YHLO). Comparative testing with the SARS-CoV-2 S1/S2 IgG assay (CLIA, DiaSorin, Liaison) found the index person and three daughters to be positive and the wife just below the cut-off (Table 1).Table 1Summary of the clinical features and laboratory results of a family of five (father, mother, and three daughters) infected with SARS-CoV-2.Age (years) and sexTravel historySymptomsOnset of symptomsTime of oropharyngeal swab (eSwab, Copan)Altona SARS-CoV-2 PCR (Ct)In-house SARS-CoV-2 PCR (Ct) (Novo Nordisk, Denmark)Time of serological testingiFlash SARS-CoV-2 N/S IgM/IgG (AU/ml)aiFlash SARS-CoV-2 N/S IgM/IgG cut-off: ≥12 AU/ml = positive.DiaSorin SARS-CoV-2 S1/S2 IgG (AU/ml)bDiaSorin SARS-CoV-2 S1/S2 IgG cut-off: ≥15 AU/ml = positive, 12 < x < 15 AU/ml = equivocal, and ≤12 AU/ml = negative.49 MaleIschgl, Austria March 3–8NoneApril 2Positive (32)NAApril 22Non-reactive/reactive (108)Positive (114)44 FemaleNone2–3 days of myalgia, arthralgia, headache, and malaiseBetween March 15 and 18April 2NegativeWeakly positive (39)April 22Non-reactive/reactive (16)Negative (9.3)18 FemaleNone2–3 days of myalgia, arthralgia, headache, and malaiseBetween March 15 and 18April 2NegativeNegativeApril 22Non-reactive/reactive (32)Positive (24.1)15 FemaleNoneMonosymptomatic ageusiaBetween March 22 and 25April 2Positive (30)NAApril 22Non-reactive/reactive (52)Positive (24.6)8 FemaleNoneRecurrent cough (known asthmatic bronchitis)April 2NegativeWeakly positive (38)April 22Non-reactive/reactive (56)Positive (55.5)SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; NA, not applicable; Ct, cycle threshold; N, nucleocapsid protein; S spike protein.a iFlash SARS-CoV-2 N/S IgM/IgG cut-off: ≥12 AU/ml = positive.b DiaSorin SARS-CoV-2 S1/S2 IgG cut-off: ≥15 AU/ml = positive, 12 < x < 15 AU/ml = equivocal, and ≤12 AU/ml = negative. Open table in a new tab SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; NA, not applicable; Ct, cycle threshold; N, nucleocapsid protein; S spike protein. This family cluster highlights several aspects of the challenges surrounding COVID-19 and SARS-CoV-2 diagnostics. The familial transmission from an asymptomatic carrier who displayed a positive SARS-CoV-2 PCR 4 weeks after becoming infected and a subsequent immunological response. The wife and three daughters, who had mild symptoms of COVID-19, presented diverse and divergent SARS-CoV-2 PCR results, yet displayed an immunological response. This family case indicates the importance of the duration of infectiousness of an asymptomatic carrier (Chan et al., 2020Chan J.F.-W. Yuan S. Kok K.H. To K.K.W. Chu H. Yang J. et al.A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.Lancet. 2020; 395: 514-523Abstract Full Text Full Text PDF PubMed Scopus (5910) Google Scholar, Huang et al., 2020Huang R. Xia J. Chen Y. Shan C. Wu C. A family cluster of SARS-CoV-2 infection involving 11 patients in Nanjing, China.Lancet Infect Dis. 2020; 20: 534-535Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar). Furthermore, it shows that symptoms and the generation of specific antibodies vary even among closely related family members, supporting the potential benefit of SARS-CoV-2 detection from a combination of nucleic acid testing and time-related serology (Fafi-kremer et al., 2020Fafi-kremer S. Bruel T. Madec Y. Grant R. Tondeur L. Grzelak L. et al.Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France.EBioMedicine. 2020; : 102915Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar, Flodgren, 2020Flodgren G.M. Immunity after SARS-CoV-2 infection, 1st update — a rapid review 2020. Norwegian Institute of Public Health, Oslo2020https://www.fhi.no/globalassets/dokumenterfiler/rapporter/2020/immunity-after-sars-cov-2-infection-1st-update-report-2020.pdfGoogle Scholar, Okba et al., 2020Okba M.N.A. Müller M.A. Li W. Wang C. Geurts van Kessel C.H. Corman V.M. et al.2-specific antibody responses in coronavirus disease 2019 patients.Emerg Infect Dis. 2020; 26: 1478-1488Crossref PubMed Scopus (1047) Google Scholar). Finally, it suggests that COVID-19 diagnostics and containment measures might benefit from grouping samples from households in order to collectively assess results and the potential need for repeat sampling (Winichakoon et al., 2020Winichakoon P. Chaiwarith R. Liwsrisakun C. Salee P. Goonna A. Limsukon A. et al.Negative nasopharyngeal and oropharyngeal swabs do not rule out COVID-19.J Clin Microbiol. 2020; 58 (e00297-20)PubMed Google Scholar). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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The paper by Pan et al. (1) reports the progression of lung involvement on CT in symptomatic patients recovering from COVID-19 pneumonia.On February 20, 2020, the first case of COVID-19 was reported in Codogno, Italy (2).On February 23, Italian health authorities ordered strict containment measures to control the infection, imposing a quarantine "red zone" in Codogno and 10 surrounding towns.Local hospitals closed and the population was quarantined at home for 14 days.Our private clinic re-opened at the end of the 14 days quarantine period.At that time, we had a high demand for chest x-rays from local asymptomatic patients or patients with vague
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