Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6–8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.

Virological assessment of hospitalized patients with COVID-2019.

Samenvatting Verwekker: Coronavirus SARS-CoV-2 Besmettingsweg: Mens-op-mens-transmissie via directe druppelinfectie (hoesten en niezen) en aerosolen tijdens aerosolvormende handelingen Incubatietijd:2-14 dagen (gemiddeld 5-6 dagen) Besmettelijke periode:Nog niet volledig bekend. In ieder geval tijdens symptomatische fase waarna virus nog langer met PCR aantoonbaar kan zijn in de keel/feces Maatregelen: Meldingsplicht groep A; bronen contactonderzoek; isolatie en verdere maatregelen op indicatie Symptomen: Milde luchtwegklachten met koorts tot ernstige pneumonie en dyspnoe

Covid-19

On 5 February 2020, in Yokohama, Japan, a cruise ship hosting 3,711 people underwent a 2-week quarantine after a former passenger was found with COVID-19 post-disembarking. As at 20 February, 634 persons on board tested positive for the causative virus. We conducted statistical modelling to derive the delay-adjusted asymptomatic proportion of infections, along with the infections' timeline. The estimated asymptomatic proportion was 17.9% (95% credible interval (CrI): 15.5-20.2%). Most infections occurred before the quarantine start.

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Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020.

As of April 2, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in >890,000 cases and >45,000 deaths worldwide, including 239,279 cases and 5,443 deaths in the United States (1,2). In the United States, 22% of the population is made up of infants, children, and adolescents aged <18 years (children) (3). Data from China suggest that pediatric COVID-19 cases might be less severe than cases in adults and that children might experience different symptoms than do adults (4,5); however, disease characteristics among pediatric patients in the United States have not been described. Data from 149,760 laboratory-confirmed COVID-19 cases in the United States occurring during February 12-April 2, 2020 were analyzed. Among 149,082 (99.6%) reported cases for which age was known, 2,572 (1.7%) were among children aged <18 years. Data were available for a small proportion of patients on many important variables, including symptoms (9.4%), underlying conditions (13%), and hospitalization status (33%). Among those with available information, 73% of pediatric patients had symptoms of fever, cough, or shortness of breath compared with 93% of adults aged 18-64 years during the same period; 5.7% of all pediatric patients, or 20% of those for whom hospitalization status was known, were hospitalized, lower than the percentages hospitalized among all adults aged 18-64 years (10%) or those with known hospitalization status (33%). Three deaths were reported among the pediatric cases included in this analysis. These data support previous findings that children with COVID-19 might not have reported fever or cough as often as do adults (4). Whereas most COVID-19 cases in children are not severe, serious COVID-19 illness resulting in hospitalization still occurs in this age group. Social distancing and everyday preventive behaviors remain important for all age groups as patients with less serious illness and those without symptoms likely play an important role in disease transmission (6,7).

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Coronavirus Disease 2019 in Children - United States, February 12-April 2, 2020.

By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID-19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID-19 has spread to 46 countries internationally. Total fatality rate of COVID-19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID-19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number (R0 ) of COVID-19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID-19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID-19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID-19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID-19 and enhance our control measures in the future.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.25748

Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures.

Coronavirus in Travelers Returning from China A group of 126 German nationals was evacuated from Wuhan to Frankfurt after screening for symptoms of Covid-19 and was to undergo a 14-day quarantine a...

https://www.nejm.org/doi/pdf/10.1056/NEJMc2001899?articleTools=true

Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China.

Angesichts der COVID-19-Pandemie wird haufig unterstellt, dass Kinder Treiber dieser Pandemie sind, und dass beim Auftreten von SARS-CoV-2 in Schulen und Kindertagesstatten ganze Gruppen, Klassen oder die gesamte Einrichtung geschlossen werden musse. Diesen Fragen wird anhand der Meldedaten in Frankfurt am Main sowie der umfangreichen Testungen der Kontaktpersonen (KP) in Schulen und Kitas nach dem Auftreten eines Indexfalles nachgegangen. Die Meldedaten wurden aus SurvStat entnommen. Die Indexfalle aus Kitas und Schulen wurden isoliert, den KP auf freiwilliger Basis eine PCR-Testung auf SARS-CoV‑2 angeboten – unabhangig davon, ob auf SARS-CoV‑2 hindeutende Symptome aufgetreten waren oder nicht. Die tiefen Nasen‑/Rachenabstriche wurden im Auftrag des Gesundheitsamtes der Stadt Frankfurt am Main durch Rettungsdienste vor Ort entnommen und nach etablierten Standards in 2 akkreditierten Instituten untersucht. Vom Marz bis zum 31.12.2020 wurden in Frankfurt am Main 22.715 COVID-19-Falle gemeldet, darunter 1588 (7,6 %) SARS-CoV-2-Nachweise bei Kindern bis 14 Jahren. Somit wurden bei Kindern bis 14 Jahren etwa halb so viele SARS-CoV-2-Nachweise gemeldet, als es ihrem Anteil an der Bevolkerung entsprochen hatte. Der Anstieg der Inzidenz bei Kindern uber die Wochen folgte zeitlich dem Anstieg der Inzidenz in der Allgemeinbevolkerung; die altersbezogene Inzidenz blieb unter der Inzidenz in der Allgemeinbevolkerung. Von der 35. bis zur 52. Kalenderwoche wurden 274 Indexfalle aus 143 Kitas und 75 Schulen gemeldet. Daraufhin wurden 7915 KP getestet. In Kitas wurde bei 4,5 % der erwachsenen KP und 2,5 % der Kinder-KP, in Schulen bei 0,9 % der Erwachsen-KP und 2,5 % der getesteten Schuler-KP SARS-CoV‑2 nachgewiesen. Pro Indexfall wurde im Mittel deutlich weniger als ein KP positiv getestet. Die Rate positiver Befunde nahm mit steigender Inzidenz in der Gesamtbevolkerung zu. Ein groserer Ausbruch trat nicht auf. Aus der Hohe und dem zeitlichen Ablauf der altersbezogenen Inzidenzen bei den Kindern in Frankfurt am Main ergaben sich keine Hinweise darauf, dass Kinder die „Treiber“ der Pandemie sind. Die untersuchten KP in Schulen und Kitas wurden nur in einem geringen Prozentsatz positiv auf SARS-CoV‑2 getestet. Bei fehlenden Hinweisen auf ein intensives Transmissionsgeschehen in den Einrichtungen kann/sollte der Besuch der KP unter Hygieneauflagen fortgesetzt werden, und es ergibt sich keine Notwendigkeit, ganze Gruppen, Klassen oder gar Einrichtungen zu schliesen.

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Children and COVID-19—Data from mandatory reporting and results of contact person testing in daycare centers and schools in Frankfurt am Main, Germany, August–December 2020

Background: In face of the coronavirus disease 2019 (COVID-19) pandemic, the question that children are also drivers of this pandemic and that groups, classes, or the entire facility should be closed when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs in schools or daycare centers is always implied. These questions were investigated using the mandatory reporting data in Frankfurt am Main and the extensive testing of contact persons (CP) in schools and daycare centers after the occurrence of an index case. Method: The reporting data were taken from SurvStat. The index cases from daycare centers and schools were isolated and the CPs were offered PCR testing for SARS-CoV­2 on a voluntary basis, regardless of whether symptoms suggestive of SARS-CoV­2 had occurred or not. Deep nasal/pharyngeal swabs were collected by paramedics on behalf of the public health department of the city of Frankfurt am Main, Germany, and tested according to established standards at two accredited institutes. Results: From March to 31 December 2020, 22,715 COVID-19 cases were reported in Frankfurt, including 1588 (7.6%) SARS-CoV­2 detections in children 14 years and younger. Thus, approximately half as many SARS-CoV­2 detections were reported in children up to 14 years of age than would have corresponded to their proportion in the population. In autumn 2020, the increase in incidence in children over the weeks followed the increase in incidence in the general population, the age-related incidence of children remained below the incidence in the general population.From week 35 to week 52, index cases were reported from 143 daycare centers and 75 schools. As a result, 7915 CPs were tested. In daycare centers, SARS-CoV­2 was detected in 4.5% of adult CPs and 2.5% of child CPs and in schools SARS-CoV­2 was detected in 0.9% of adult CPs and 2.5% of student CPs tested. On average, less than 1 CP tested positive per index case. The rate of positive findings increased with increasing incidence in the overall population. No major outbreak occurred. Discussion: Regarding the level and timing of age-related incidences among children in Frankfurt am Main, there was no evidence that children were the drivers of the pandemic. Only a small percentage of the examined CPs in schools and daycare centers tested positive for SARS-CoV­2. In the absence of evidence of intense transmission in the facilities, CP attendance can/should continue under hygiene conditions and there is no need to close entire groups, classes, or even facilities.

[Children and COVID-19-Data from mandatory reporting and results of contact person testing in daycare centers and schools in Frankfurt am Main, Germany, August-December 2020]./ Kinder und COVID-19: Kontaktpersonen-Surveillance in Frankfurter Kitas und Schulen (August bis Dezember 2020).

Background The measures taken to combat the COVID-19 pandemic have severely restricted the opportunities for the development of children. This paper will discuss the reporting data of children and the public health department's activities against the background of the restrictions of school and leisure time offers as well as sports and club activities. Materials and methods Reporting data from Frankfurt am Main, Hesse, were obtained using a SURVStat query for the calendar weeks 10/2020-28/2021 and from SURVNet (until 30 June 2021). Contact persons (CP) of SARS-CoV‑2 positive persons from schools and daycare centers were screened for SARS-CoV‑2 by PCR test. These results and those of rapid antigen testing, which has been mandatory for schoolchildren since April 2021, are presented. Results Until Easter break, the age-related seven-day incidence values per 100,000 for children 14 years of age and younger were lower than the overall incidence; it was only higher after rapid antigen-testing was mandatory for schoolchildren. Most children with SARS-CoV‑2 had no or mild symptoms; hospitalization was rarely required and no deaths occurred. Contact tracing in schools and daycare centers found no positive contacts in most cases and rarely more than two. Larger outbreaks did not occur. Conclusion SARS-CoV‑2 infections in children appear to be less frequent and much less severe than in adults. Hygiene rules and contact management have proven themselves effective during times with high incidences in the local population without mandatory rapid antigen testing - and even with a high proportion of variants of concern (alpha and delta variants) in Germany. Against this background, further restriction of school and daycare operations appears neither necessary nor appropriate.

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[Children in the COVID-19 pandemic and the public health service (ÖGD) : Data and reflections from Frankfurt am Main, Germany]

Die Masnahmen zur Bekampfung der COVID-19-Pandemie haben die Entwicklungsmoglichkeiten von Kindern stark eingeschrankt. In dem Beitrag werden die Meldedaten von Kindern und die Aktivitaten des Gesundheitsamtes vor dem Hintergrund der Einschrankungen der Schul- und Freizeitangebote sowie der Sport- und Vereinssportangebote diskutiert. Meldedaten aus Frankfurt am Main wurden mittels einer SURVStat-Abfrage (KW 10/2020–KW 28/2021) und aus SURVNet (bis 30.06.2021) ermittelt. Kontaktpersonen (KP) von SARS-CoV-2- positiv gemeldeten Personen aus Schulen und Kitas wurden mittels PCR-Test auf SARS-CoV‑2 untersucht. Die Ergebnisse sowie die der seit April 2021 fur Schuler verpflichtenden Antigenschnelltests werden vorgestellt. Die altersbezogenen 7‑Tage-Inzidenzen der Kinder bis 14 Jahre lagen vor der Einfuhrung der Testpflicht fur Schuler stets unter der Gesamtinzidenz, danach daruber. Die meisten Kinder mit SARS-CoV‑2 hatten keine oder nur milde Symptome; eine Hospitalisierung war selten erforderlich, Todesfalle traten nicht auf. Bei den Untersuchungen der KP in Schulen und Kitas wurden meist keine und nur selten mehr als 2 positive KP gefunden. Grosere Ausbruche traten nicht auf. SARS-CoV-2-Infektionen bei Kindern sind offenbar seltener und deutlich weniger schwer als bei Erwachsenen. Grosere Ausbruche konnten im Setting Schule und Kita zuverlassig verhindert werden. Die AHA + L-Regeln und das Kontaktmanagement haben sich bewahrt – auch bei hohen Inzidenzen in der lokalen Bevolkerung ohne Schnelltestpflicht und selbst bei einem hohen Anteil von besorgniserregenden Virusvarianten (Alpha und Delta) in Deutschland. Eine weitere Einschrankung des Schul- und Kitabetriebs scheint deshalb weder erforderlich noch angemessen zu sein.

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Antoni Walczok

Papers

Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China.

Children and COVID-19—Data from mandatory reporting and results of contact person testing in daycare centers and schools in Frankfurt am Main, Germany, August–December 2020

[Children and COVID-19-Data from mandatory reporting and results of contact person testing in daycare centers and schools in Frankfurt am Main, Germany, August-December 2020]./ Kinder und COVID-19: Kontaktpersonen-Surveillance in Frankfurter Kitas und Schulen (August bis Dezember 2020).

[Children in the COVID-19 pandemic and the public health service (ÖGD) : Data and reflections from Frankfurt am Main, Germany]

Kinder in der COVID-19 Pandemie und der Öffentliche Gesundheitsdienst (ÖGD)