On 2019-07-21 06:26:16, user Guyguy wrote:

ENGLISH

OFFICIAL PRESS RELEASE RELATED TO THE EPIDEMIC OF EBOLA VIRUS DISEASE IN EASTERN DRC

1. The Democratic Republic of the Congo takes note of the statement by the World Health Organization (WHO) that the current epidemic is a public health emergency of international concern and endorses the recommendations of the WHO Director-General not to impose travel and trade restrictions and stigmatization of populations already in need of assistance.

2. The Democratic Republic of the Congo reiterates its strong commitment to continue the response to the Ebola virus epidemic and to strengthen cross-border control and control of major internal roads to ensure that no cases are omitted or escapes from the surveillance teams.

3. The response to the Ebola Virus Disease outbreak is now under the direct supervision of His Excellency the President of the Republic. To this end, it was decided to entrust the responsibility of the Technical Secretariat of the Multisectoral Committee to a team of experts under the direction of Professor Jean Jacques MUYEMBE TAMFUM.

4. This team of experts is responsible for coordinating all the activities for implementing the Ebola response strategy. The Technical Secretariat is in charge of putting in place all the innovative measures that are urgent and indispensable for the rapid control of the epidemic.

5. His Excellency the President of the Republic reassures the Congolese people and the neighboring countries that the measures currently taken in connection with the response to the Ebola Virus Disease in the DRC are likely to eradicate this epidemic.

Kinshasa, July 20th, 2019.

Source: Office of the President of the Democratic Republic of the Congo

********************************<br /> FRENCH

COMMUNIQUE OFFICIEL EN RAPPORT AVEC L'EPIDEMIE DE LA MALADIE A VIRUS EBOLA A L'EST DE LA RDC

1. La République Démocratique du Congo prend acte de la déclaration de l'Organisation Mondiale de la Santé (OMS) faisant de l'épidémie actuelle une urgence de santé publique de portée internationale et fait siennes les recommandations du Directeur Général de l'OMS de ne pas imposer des restrictions des voyages et de commerce ainsi que la stigmatisation des populations se trouvant déjà dans le besoin d'une assistance.

2. La République Démocratique du Congo réitère son ferme engagement à poursuivre la riposte à l'épidémie de la Maladie à virus Ebola et à renforcer le contrôle transfrontalier et celui des principales routes internes afin de veiller à ce qu'aucun cas ne soit omis ou n'échappe aux équipes de surveillance.

3. La conduite de la riposte à l'épidémie de la Maladie à virus Ebola se fait désormais sous la supervision directe de Son Excellence Monsieur le Président de la République. A cet effet, il est décidé de confier la responsabilité du Secrétariat Technique du Comité Multisectoriel à une équipe d'experts, sous la direction du Professeur Jean Jacques MUYEMBE TAMFUM.

4. Cette équipe d'experts a pour mission d'assurer la coordination de l'ensemble des activités de mise en oeuvre de la stratégie de riposte à la Maladie à virus Ebola. Le Secrétariat Technique est chargé de mettre en place toutes les mesures innovantes urgentes et indispensables au contrôle rapide de l'épidémie.

5. Son Excellence Monsieur le Président de la République rassure les populations congolaises et les pays voisins que les mesures actuellement prises en rapport avec la riposte à la Maladie à virus Ebola en RDC sont de nature à éradiquer cette épidémie.

Fait à Kinshasa, le 20 juillet 2019.

Source: Cabinet du Président de la République Démocratique du Congo

On 2019-07-18 18:38:41, user Guyguy wrote:

EVOLUTION OF THE EBOLA EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI

Show solidarity with the Congolese people in the 10th Ebola outbreak declared a health emergency of international concern: understand a qualitative study of variables of hospital activities on infection control practices in Kinshasa city

Wednesday, July 17, 2019

Statement Ebola outbreak in DRC as a health emergency of international concern

Following the recommendations of the international expert committee, WHO declared on Wednesday, July 17, 2019, that the Ebola epidemic in the DRC was a health emergency of international concern.<br /> The Ministry of Health accepts the evaluation of the expert committee. The ministry hopes that this decision is not the result of the many pressures from different stakeholder groups who wanted to use this statement as an opportunity to raise funds for humanitarian actors despite the potentially harmful and unforeseen consequences for the affected communities that depend on them. greatly from cross-border trade for their survival.<br /> While the Government continues to openly share with partners and donors the way in which it uses the funds received, we hope that there will be greater transparency and accountability of humanitarian actors in their use of funds to respond. to this Ebola outbreak.<br /> The Ebola epidemic is above all a public health crisis that requires a response by actors with real technical expertise. However, the main difficulty is that this epidemic occurs in an environment characterized by problems of development and shortcomings of the health system.<br /> Furthermore, we regret that after spending almost a year in this epidemic, certain groups of people in the community continue to adopt irresponsible behavior that causes the geographical spread of the virus. It is important to remember that in the cases of Goma and Uganda, the patients knew that they were at risk but refused to respect the health recommendations and deliberately traveled to another area. The Government will consider what steps need to be taken to prevent these high-risk groups from continuing to spread the epidemic in the region.

Follow-up of the situation of the pastor's contacts who traveled to Goma<br /> Vaccination around the confirmed Goma case continues at the Afia Himbi Health Center in the Goma Health Zone. All contacts in the city were found in less than 72 hours, including the motorcycle taxi driver that the pastor had used to get to the health center. The response teams from Beni and Butembo continue the investigations to trace the pastor's journey and identify his contacts in these two cities.

The epidemiological situation of the Ebola Virus Disease dated 16 July 2019:<br /> Since the beginning of the epidemic, the cumulative number of cases is 2,522, 2,428 confirmed and 94 probable. In total, there were 1,698 deaths (1,604 confirmed and 94 probable) and 717 people cured.<br /> 374 suspected cases under investigation;<br /> 10 new confirmed cases, including 6 in Beni, 2 in Mabalako, 1 in Katwa and 1 in Mangurujipa;<br /> 10 new confirmed cases deaths:<br /> 5 community deaths, including 3 in Beni, 1 in Mabalako and 1 in Mangurujipa;<br /> 5 deaths at Ebola Treatment Center (ETC) including 4 in Beni and 1 in Katwa;<br /> 7 people cured out of Mabalako Ebola Treatment Center.

No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 136 (5% of all confirmed / probable cases), including 41 deaths.

Deaths and cures data recorded in ETCs for the period 9-11 July 2019 are now available and have been added to the summary table.<br /> In total, 12 deaths were recorded in ETC during this period:<br /> 7 deaths at the ETC de Beni<br /> 3 deaths at Butembo ETC<br /> 2 deaths at Katwa ETC<br /> In total, 7 cures were discharged from ETC during this period:<br /> 5 cured at Butembo ETC<br /> 1 cured at the ETC of Beni<br /> 1 cured at Katwa ETC

75,697,081 Controlled people<br /> 80 entry points (PoE) and operational health checkpoints (PoC).

Source: Ministry of Health press team on the state of the response to the Ebola epidemic in the Democratic Republic of the Congo

On 2019-09-30 05:24:02, user Guyguy wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT 25 SEPTEMBER 2019

The epidemiological situation of the Ebola Virus Disease dated September 25, 2019

Thursday, September 26, 2019

Since the beginning of the epidemic, the cumulative number of cases is 3,178, of which 3,066 confirmed and 112 probable. In total, there were 2,126 deaths (2014 confirmed and 112 probable) and 981 people healed.

• 483 suspected cases under investigation; <br /> • 3 new confirmed cases, including: <br /> • No cases in North Kivu; <br /> • 3 in Ituri, including 2 in Mandima and 1 in Mambasa; <br /> • 4 new confirmed deaths, including; <br /> • 1 community death in Ituri in Mandima; <br /> • 3 deaths of confirmed cases in North Kivu, including 2 in Katwa and 1 in Beni; <br /> • 1 person cured out of CTE in North Kivu in Butembo; <br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 160 (5% of all confirmed / probable cases), including 41 deaths. <br /> NEWS <br /> Six people from Mambasa cured of Ebola Virus Disease out of Komanda CTE in Ituri * <br /> • The Ebola Treatment Center (ETC) in Komanda, Ituri province, unloaded on Thursday, September 26, 2019, six people cured of Ebola Virus Disease, all from Mambasa; <br /> • For the director of the Komanda CTE, Claude Banga Lonema, this treatment center receives patients from the Nyakunde and Komanda health zones, as well as from Mambasa well before the construction of its CTE, which has become functional for almost a week; <br /> • For the director of the CTE of Komanda, Dr. Claude Banga Lonema, all these cures are the work of a whole team, including medical and paramedical staff, psychosocial teams, nutritionists and hygienists and guards, to whom he is grateful for all their efforts in this day-to-day treatment center, as well as dedication and their apostolate; <br /> • The coordinator ai of the Subcommittee on Response and Chief Medical Officer of the Komanda Health Zone, Dr. Faustin Singo Ngozo, said on this occasion that the success and success of Ebola Virus Disease is an asset for everyone in the response. This success must be shared, because if surveillance does not work, there will always be notification of deaths. The presence of cures at the Komanda CTE shows that epidemiological surveillance has been successful in detecting cases in a timely manner and has enabled the care physicians to have sufficient time to treat these patients. To this end, he recommended mutual support among all the teams in the response to push him out of the way to harm the epidemic, which he said has lasted too long, to continue working with the same momentum. He also asked the six healings to help the response in sensitizing everyone in his respective environment. Military healing, he said, is a resource that can educate his colleagues to end this epidemic; <br /> • Among the Mambasa healers who were discharged from the Komanda Treatment Center were an 8-year-old girl, a man in uniform, including the Armed Forces of the Democratic Republic of the Congo, and the village chief of Makoko II, a village in strong resistance. The latter two promised to raise awareness about Ebola Virus Disease in their respective communities; <br /> • This triumphal exit from the six healings of Mambasa, an area still showing resistance against EVD, was made in the presence of the few partners, namely the delegates of WHO and UNICEF: <br /> • Beginning with the prayer, this ceremony also ended with prayer and a family photo between the cures and the teams of the response in this ETC; <br /> • Immediately after, their exits from the CTE of Komanda, the cured were accompanied by the teams of the response to Mambasa, their respective health zone, where a festive atmosphere awaited them; <br /> • The Komanda CTE is located in the Mangiva Health Area, precisely in Makayanga village in the health zone of Komanda, 100 km from the Mambasa health zone.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding). <br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

VACCINATION <br /> • Expanded ring vaccination around 2 confirmed cases in the Mataba Health Area in Kalunguta, North Kivu. In addition, two other vaccination rings, in the same health zone, are waiting to be opened in Lisasa and Kabasha Health Zones; <br /> • Since the beginning of vaccination on August 8, 2018, 228,430 people have been vaccinated; <br /> • The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

MONITORING AT ENTRY POINTS <br /> • Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 98,818,462; <br /> • To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

LEXICON <br /> • A community death is any death that occurs outside a #Ebola Treatment Center. <br /> • A probable case is a death for which it was not possible to obtain biological samples for confirmation in the laboratory but where the investigations revealed an epidemiological link with a confirmed or probable case.

On 2019-10-02 02:06:42, user Guyguy wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT 29 SEPTEMBER 2019<br /> The epidemiological situation of the Ebola Virus Disease dated September 29, 2019<br /> Monday, September 30, 2019

• Since the beginning of the epidemic, the cumulative number of cases is 3,191, of which 3,077 are confirmed and 114 are probable. In total, there were 2,133 deaths (2019 confirmed and 114 probable) and 991 people healed . <br /> • 346 suspected cases under investigation; <br /> • 3 new confirmed cases, including: <br /> • 1 in North Kivu in Kalunguta; <br /> • 2 in Ituri, including 1 in Mambasa and 1 in Mandima; <br /> • 4 new confirmed deaths in Ituri, including: <br /> • 1 community death in Ituri 1 in Mandima; <br /> • 3 confirmed deaths in CTEs in Ituri, including 2 in Mambasa and 1 Komanda; <br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 160 (5% of all confirmed / probable cases), including 41 deaths.

Synthesis of epidemiological data at week 39 (from 23 to 29/09/019)

• Number of probable new cases: 3 <br /> • Number of new confirmed cases: 20 <br /> • Number of new healings: 16 <br /> • Number of new deaths: 12 <br /> • Community: 4 <br /> • Confirmed deaths: 8

NEWS

Local providers of 17 silent and hard-to-reach health areas in Mambasa in Ituri sensitized on EVD

• One hundred and two local providers of 17 silent and hard-to-reach health areas in the Mambasa Ebola Virus Disease Response (EVD) sub-coordination were sensitized from 29 to 30 September 2019 in women's ward in Mambasa in Ituri province on this disease;

• This took place during a briefing day for the purpose of helping to stop the transmission of Ebola Virus Disease in this sub-coordination in order to prevent its spread to other health zones. , DRC provinces and neighboring countries;

• This day also had the objective of setting up a functional alert system in the community and in the health structures of the target health areas and a communication system allowing a rapid response in case of notification of a validated alert. , a new confirmed or probable case and accelerate ownership of the response by communities, their leaders and local health system actors;

• These local providers were trained on EVD basics, early definitions / detections of cases and actions to be taken, as well as escalation of alerts, risk communication and community engagement. They were also trained on dignified and safe burial (DHS), active case finding, community-level monitoring tools and reporting system, risk communication and community engagement;

• Awareness Day was opened by Mambasa Territory Administrator Mr. Idriss Koma Kukodila in the presence of the Deputy General Coordinator for Ebola Response to the Epidemic, Dr. Justus Nsio Mbeta, the Physician the coordination of the Mambasa Health Zone, representing the Mambasa sub-coordinator of the response and the field coordinators of WHO and UNICEF;

• The sub-coordination of the Mambasa response includes 3 health zones, including Mambasa, Lolwa and Mandima, and 28 health areas, including 6 hot spots reporting cases within 14 days. These include Binase, Lolwa, Mambasa, Salama, Mandima and Some;

• The 17 health areas are: Banana, Tabala, Bandishende, Makoko II, Epulu, Salate, Molokai, Bukulani, Akokora, Pede, Bakaiko Kenya, Nduye, Bongupanda, Malembi, Bahaka, Lolwa and Some. These are health areas that do not report EVD alerts and are areas of difficult access and insecurity.

VACCINATION

• Since vaccination began on August 8, 2018, 230,489 people have been vaccinated;

• The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

MONITORING AT ENTRY POINTS

• Since the beginning of the epidemic, the total number of travelers checked (temperature measurement) at the sanitary control points is 100,607,920;

• To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding). <br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

On 2019-10-10 12:58:07, user GuyguyKabundi Tshima wrote:

EPIDEMIOLOGICAL SITUATION

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT OCTOBER 07, 2019<br /> Tuesday, October 08, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,206, of which 3,092 are confirmed and 114 are probable. In total, there were 2,143 deaths (2029 confirmed and 114 probable) and 1006 people healed.<br /> 443 suspected cases under investigation;<br /> 1 new case confirmed at CTE in Ituri in Mandima;<br /> 1 new confirmed death in North Kivu in Mabalako;<br /> 10 people were cured from the CTE, including 7 in Ituri in Komanda and 3 in North Kivu, including Beni, 1 in Katwa and 1 in Mabalako;<br /> No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths.

No more confirmed cases of EVD at Butembo CTE<br /> - The Butembo Ebola Treatment Center (CTE) in North Kivu no longer has a confirmed case of Ebola Virus Disease;<br /> - The last two confirmed cases supported in this CTE have been released since Sunday, October 07, 2019 and have been reintegrated this Tuesday, October 08, 2019 in their respective communities by the teams of the response to the Virus Disease #Ebola of the psychosocial care. These cases are respectively health zones of Biena and Kayna;<br /> - Miss Ornella Bwira Zawadi, psychosocial supervisor at Butembo CTC, explains the psychosocial care at the Treatment Center. The Butembo CTE uses 17 psychologists subdivided into four blocks of tasks. These are triage supervisors, suspected cases, confirmed cases and accompanying village;<br /> - In the triage center, the psychologist ensures the awareness of newly admitted CTE cases. These new cases are normally 72 hours in the ETC and are taken on the 1st and the last day;<br /> - From the first day, the psychologist announces the result to the patients, its clinical evolution and its state. The patient who is positive is moved from the suspect's room to the confirmed block, while the patient who is negative until the third day remains in the suspected cases;<br /> - When the person is confirmed Ebola case, the psychologist is responsible for announcing his result, to make him aware of its evolution and life at the CTE. He asks him questions about his career in order to facilitate the follow-up of contacts;<br /> - It also monitors the confirmed case daily and ensures the relay between the patient and his family;<br /> - The accompanying person allows the good collaboration between the other CTE provider teams with the patient. It transmits various information of the patient, as well as its evolution to the other teams of the CTE;<br /> - Thereafter, intervenes the reintegration of suspected or confirmed cases cured and removed from the CTE. The psychiatrist accompanies him in his community. He educates his community and his family, explaining that the person who has been cured of Ebola is not dangerous and can not infect anyone else with the Ebola Virus Disease;<br /> - This Tuesday, October 08, 2019, Butembo CTE also released non Ebola people who were admitted to CTE as suspected cases.

VACCINATION

• A vaccination ring was opened around the confirmed case of 06 October 2019 in the Oicha health zone in Tenambo, North Kivu;
• Continuation of vaccination around the last case of 04 October 2019 in Andindulu village in the Lolwa health zone in Ituri;
• Continuation of the vaccination of newly recruited front-line staff in the Reference Hospitals of Katwa and Kyondo Health Zones;
• Launch of Local Polio Immunization Days integrated with vitamin A supplementation and mebendazole deworming in 17 ZS of Butembo Antenna, most of which are Ebola virus-infected areas;
• Since vaccination began on 8 August 2018, 235,389 people have been vaccinated;
• The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

MONITORING AT ENTRY POINTS

• Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 103,567,829 ;
• To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

On 2019-10-16 12:34:53, user GuyguyKabundi Tshima wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS OF OCTOBER 10, 2019<br /> Friday, October 11, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,210, of which 3,096 confirmed and 114 probable. In total, there were 2,146 deaths (2032 confirmed and 114 probable) and 1028 people healed.<br /> 422 suspected cases under investigation;<br /> 2 new case confirmed at CTE in Ituri in Mandima;<br /> 2 new confirmed deaths, including 1 in North Kivu in Mabalako and 1 in Ituri in Mandima;<br /> 1 person healed out of CTE in Ituri in Mambasa;<br /> No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths.

NEWS

President Félix-Antoine Tshisekedi Tshilombo submits to sanitary control for the prevention of #Ebola Virus Disease at Beni Airport<br /> - The Head of State, Coordinator of the Multisectoral Committee for the Ebola Virus Epidemic Response (CMRE), President Félix-Antoine Tshisekedi Tshilombo and his delegation were welcomed on Thursday, October 10, 2019 by the monitoring team at the entry points / sanitary control at Mavivi Airport in Beni, North Kivu Province. President Tshisekedi and his team have gone through all stages of health control at this point of entry to prevent Ebola Virus Disease;<br /> - The Ebola Virus Epidemic Response Coordination Team and a few members of the CMRE Technical Secretariat have been staying in Mambasa, Ituri province since Wednesday. It is in this part of the Democratic Republic of Congo that the last confirmed cases of #Ebola Virus Disease are concentrated;<br /> - This team, made up of the different experts in Ebola Virus Disease, has moved closer to Mambasa to coordinate closely the activities of the response;<br /> - Since they have been there, several activities have taken place, among which the release of 5 cured people from the ETC and a big meeting with all the partners of the response present in this sub-coordination. This meeting stems from the orientations to end the epidemic in this part of the DRC.

VACCINATION

• The symbolic vaccination of the local chief resisting the vaccination of Butama in the health zone of Mambasa in Ituri. Also in Ituri, continued immunization around two confirmed cases from 07 and 08 August 2019 in Biakato mine in Mandima with low participation due to community reluctance;
• Immunization of front-line staff continued in the Kyondo and Kayna Reference Hospitals in North Kivu;
• Continuation of Local Polio Vaccination Days integrated with Vitamin A supplementation and Mebendazole deworming in 17 health zones at the Butembo antenna in North Kivu;
• Since vaccination began on August 8, 2018, 236,772 people have been vaccinated;

MONITORING AT ENTRY POINTS

• Since the beginning of the epidemic, the total number of travelers checked (temperature measurement ) at the sanitary control points is 104,765,252 ;
• To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

On 2019-11-13 01:31:13, user Guyguy wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT NOVEMBER 11, 2019

Tuesday, November 12, 2019<br /> • Since the beginning of the epidemic, the cumulative number of cases is 3,287, of which 3,169 confirmed and 118 probable. In total, there were 2,193 deaths (2075 confirmed and 118 probable) and 1067 people cured.<br /> • 545 suspected cases under investigation;<br /> • No new confirmed cases;<br /> • No new deaths of confirmed cases have been recorded;<br /> • No cured person has emerged from ETCs;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths;

NEWS

Organization of a press conference in Goma on the introduction of the second Ebola vaccine in the Democratic Republic of Congo

• The coordination of the epidemic response to Ebola Virus Disease organized this Tuesday, November 12, 2019, jointly with the International Non-governmental Organization Médecins Sans Frontières of France (MSF / France), a press conference on introduction of the second Ebola vaccine, Johnson & Johnson, at the Karibu Hotel in Goma, capital of North Kivu Province;<br /> • During this press conference, the coordinator of the response, Prof. Steve Ahuka Mundeke, announced that vaccination with this second vaccine will start on Thursday, November 14, 2019 in two health areas of Karisimbi in Goma, including Majengo and Kahembe. The beginning of the vaccination will thus precede the official launch of the introduction of this vaccine which will intervene in the days to come;<br /> • This vaccine will be administered intramuscularly in two doses with an interval of 56 days. It targets adults and children over twelve months old. It has a strong immune response and its dose has the advantage of increasing this response by making it more sustainable in order to protect populations against a possible Ebola outbreak, according to a member of the consortium that took care of the study of this vaccine, Dr Hugo Kavunga, project manager INRB, member of the consortium;<br /> • Everyone is eligible for this vaccine, including children over the age of one, even pregnant and lactating women. In addition, for women of childbearing age, they will be offered a pregnancy test. Those who do not want it, will always be vaccinated. Pregnant women will be followed, said Vaccine Project Coordinator at MSF / France, Dr Véronique Urbaniak;<br /> • The choice of vaccination site was made after several studies and it is in order to protect the population against possible epidemics that Majengo and Kahembe were selected;<br /> • The vaccine is called Ad26.Zebov / MVA-BN-Filo. It is of Belgian-American origin and is named Johnson and Johnson. It has already been used in Sierra Leone in West Africa, Uganda and soon Rwanda. This second vaccine complements the first in-use vaccine in belt strategy and has already saved more than 3,000 people to date;<br /> • In addition to the speakers, two other members of the consortium took part in the press conference, including the London Shool Project Investigator Dr. Dan Baush and the Epicenter's Immunization Coordinator Marie Burton.

VACCINATION

• Preparation of the launch of the 2nd Ebola vaccine, J & J in Kahembe and Majengo Health Areas in Karisimbi, Goma, North Kivu;<br /> • 37 participants, including 4 high-risk contacts, 6 contacts, 7 CPs and 20 front-line staff, were vaccinated from the confirmed case of 09 November 2019 in the Bingo Health Area in Mabalako, North Kivu;<br /> • Since vaccination began on August 8, 2018, 250,622 people have been vaccinated;<br /> • The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

MONITORING AT ENTRY POINTS

• Disruption of activities at PoC VIRENDI (SC BUTEMBO) following clashes between FARDC soldiers and incivists not otherwise identified.<br /> • Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 116,184,525 ;<br /> • To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic

On 2019-11-08 19:03:54, user Rachel Couban wrote:

looking forward to reviewing the definition :)

On 2020-02-03 16:29:21, user Sarah wrote:

Hi, I'm not sure why you use the study 3 (Read et al.2020) estimate at 3.8. Their estimate is 3.11 (95%CI, 2.39-4.13). Is it an error?

On 2020-02-10 07:08:01, user ScientistCN wrote:

Only 1099 patients were analyzed, how can we get the significant figure to 0.01%?

On 2020-02-15 21:55:51, user Nate wrote:

It does need to be pointed out that this is Pre-Print at this point in time. It still needs to go through peer-review, etc., to be published.

That said, if this research is borne out/validated then this is pretty problematic news. The Chinese Government gave an R0 value of 2.6-2.9 or something like that, and also has publicly said the mortality rate is similar to the 2006 SARS outbreak (which had a lower R0 of something like 1.9 or something (possibly lower) ultimately. Assuming these figures are more accurate, If the Chinese Government is either not finding or hiding the number of cases but not the number of deaths, it actually may be good news, as the mortality rate would be considerably lower. However if they are wrong about or lying about both figures and it is both more contagious and more deadly, this could be a pretty serious epidemic/pandemic. If they, for instance are underestimating or underreporting the mortality rate by about .5 deaths per 1000 (I believe that’s the metric I’ve seen), the mortality rate would be roughly that of the 1918 Spanish Flu. Now, we are far better at treating symptoms now and preventing person to person spread of disease as we were in 1918, as well as developing vaccines. We have a lot of developed treatments that could be effective in minimizing symptoms or fighting the disease as well, even short of a currently viable cure/particularly effective treatment.<br /> However, that R0 value, if anywhere close to on target is pretty alarming. Even if the actual value is halfway between China’s figures and this study’s figures, and even if it were merely as deadly as SARS was.

Still, this isn’t an official figure yet. This isn’t even published, we don’t know how much other research will validate this number or contest it. So don’t panic based on a pre-print article. This probably has more value being available for other researchers, whom seeing other people’s figures, or methodology could benefit in their own research or methodology, and public heath officials who need to try to assess what a worst case scenario may look like. If these figures are accurate, they would be alarming. Even somebody who can read statistics and the language correctly in shouldn’t simply take something like this as fact, until it gets through peer review, other experts evaluate it once it’s published, and other figures start to align with their findings. I engaged in speculation, as it is really concerning should these figures be correct, and an interesting conversation to engage in. However, I am not credentialed in epidemiology, public health, or medicine. You should listen to experts and public health officials, over then speculation of somebody like myself. I am discussing the implications of this if true, not rendering an expert opinion.

On 2020-02-29 22:14:11, user Meat house man wrote:

Thank you for this in this dynamic situation..let me know which journal it gets published in.<br /> I agree with your conclusion re R0..

On 2020-02-19 22:23:35, user hvoltbb wrote:

There is a typo in the abstract "The updated basic reproductive number was found to be 2.12 on average with and a 95% credible interval of [2.04, 2.18]. ".<br /> It should be "and with". I was typing so fast on my laptop that words switched places. It will not get fixed in the second version, because the revision has already been uploaded.

On 2020-03-05 21:03:21, user Arturo Tozzi cns wrote:

CROSS-REACTIVITY BETWEEN COVID-19 AND CHILDHOOD VACCINES?

One speculation for the lower SARS clinical severity in children is that cross-protective antibodies were elicited in children as a response to one of their childhood vaccines.<br /> A 2007 paper (on mice immunised with various vaccines) states that children's vaccines do not induce cross reactivity against SARS-CoV

https://www.ncbi.nlm.nih.go...

However, the above-mentioned paper is affected by several bias.

Therefore, would it be feasible to look for cross-correlations between the RNA and proteic sequences of the NCOV 2019 and the immunogenic epitopes of the vaccines administeded to chinese children? If a correlation does exist, it could be possible to vaccinate the whole sensitive population.

Arturo Tozzi<br /> Center for Nonlinear Science, Department of Physics, University of North Texas, Denton, Texas, USA<br /> tozziarturo@libero.it<br /> Arturo.Tozzi@unt.edu

Gennaro D'Amato<br /> Division of Respiratory and Allergic Diseases, Department of Chest Diseases, High Specialty A. Cardarelli Hospital, Napoli, Italy<br /> Medical School of Specialization in Respiratory Diseases, University on Naples Federico II.<br /> gdamatomail@gmail.com

On 2020-03-09 02:23:08, user Angel Paternina-Caicedo wrote:

Great to see more data on the COVID-19 epidemic. The following comment does not deal with study methods. Despite the study appears methodologically sound, the Supplementary Material is not complete at this point, and this is needed for a full assessment.

This comment focus on the broad interpretation on the results of this study. The results of this study does not support the conclusion that the disease has been contained in Wuhan.

The study does not show evidence of no circulation in Wuhan after containment measures.

According to the results of this study, these isolation and quarantine measures have been effective to curve down and delay the peak attack-rate. Despite this, so far, there is no evidence that the final peak attack-rate will be lower after these measures, meaning, the final tally of infected population may not differ with or without these containment measures. The epidemic is only a few months old, and COVID-19 is still circulating in Wuhan and elsewhere in the world.

Also, the economic costs of shutting down the entire city are not quantified yet. And this experience is unlikely to be able to replicate in most of the world.

The conclusion that COVID-19 is contained after these strong measures in Wuhan, based on results of this study, are misleading. Notwithstanding, the delay to achieve the peak attack rate may give some time for the development and testing of a vaccine.

On 2020-03-12 20:49:50, user personfromreddit wrote:

Thank you for the well-designed and informative experiments and paper. The implications are critically important to managing COVID-19 patients and preventing further outbreak. However, in seeking publication for this paper I strongly recommend that the authors bolster their discussion -- specifically on the topic of in vitro vs. in vivo aerosolization. I am not a virologist, but I understand that just because SARA-CoV-2 can be aerosilized in similar systems that you used in your paper, that it may not mean there is clinical aerosolization and viral spread. While you touch on this in the paper and state that it is "plausible" that aerosol may contribute to spread, I think there needs to be more nuance to this discussion as to how likely this may be. To my understanding there are notable cases where in vitro systems such as the one in this study have found steady viral aerosols, but clinical aerosolization was not significant enough to present a means of viral spread (i.e. ebola).

I think discussing the topic of aerosolization in more detail are especially important for this paper during this time period -- one where many non-virologists and laypeople are reading high-brow virology literature. A more careful and detailed discussion of the implications of these findings will help prevent undue interpretations of these results.

On 2020-03-13 18:45:34, user naturebroad wrote:

What about Formica, laminates, butcher block, stone (soapstone, granite, marble, etc.), quartzite, solid surface kitchen countertops (acrylic resin, polyester resin or a combination of the two that is combined with filler,etc.),

On 2020-03-14 16:18:13, user Donna Lovitt Wells wrote:

In the dental profession aerosols are created pretty much every time a dental hygienist treats a patient or dentist uses a high speed drill. Would these professions be at high risk even if they use all appropriate PPE given that the aerosols stay in the air?

On 2020-03-16 16:32:43, user Bill Keevil wrote:

Although not peer reviewed yet, this work is not surprising because we showed long term survival of the similar coronavirus 229E on plastics, ceramics, stainless steel and glass for 4-5 days; the virus was inactivated on copper in just minutes and its RNA destroyedhttps://mbio.asm.o.... Another group showed SARS survived 5 days on stainless steel. We and others also showed flu survives several days. Implications are that in a closed environment a potentially infectious aerosol of small particle size can remain suspended in air for some time before landing on surfaces – hence being outdoors or opening windows is probably a good thing. It might question whether the 2 metre gap between people is sufficient in a confined space. As I have said before, survival of coronaviruses for days on touch surfaces (not the 2 hours cited by some advisers) is a hygiene risk, and it is difficult to avoid touching door handles, stair rails, public touch screens etc. It re-emphasises the need for good personal hygiene such as washing hands rigorously throughout the day, or using an alcohol hand gel, and avoid touching the eyes, nose and mouth.

Because this is a pre-print it is difficult to know exactly what they have done. Clearly they are using a different virus and culturing in Vero-E6 kidney cells while we used MRC-5 lung cells. An important difference may be that in their 2003 MERS paper they used 100ul culture onto unspecified size surfaces (“washers”) –McMaster-Carr, USA); for the new paper where they say they used 50ul of virus then we know that this can take a long time to dry out. Copper alloys kill bacteria and viruses when dry due to the inactivation mechanisms we have published. Our method to simulate hand contact uses 20ul onto 1 square cm, spread over the surface and then dries out in several minutes; sometimes we use 1ul when we have high concentrations of pathogen available.

Perhaps more importantly, our cells were maintained in minimal essential medium (MEM) supplemented with 1mM GlutaMax-1*, nonessential amino acids, and 5% fetal calf serum and incubated at 37°C and 5% CO2. Their cells were maintained in Dulbecco’s Modified Eagle Medium (DMEM; Sigma) supplemented with 2% fetal calf serum (Logan), 1 mM L-glutamine (Lonza), 50 U/ml penicillin and 50 µg/ml streptomycin (Gibco).

*(GlutaMAX™-1 (Gibco), L-alanyl-L-glutamine, is a dipeptide substitute for L-glutamine. GlutaMAX™-1 can be used as a direct substitute for L-glutamine at equimolar concentrations in both adherent and suspension mammalian cell cultures with minimal or no adaptation. GlutaMAX™-1 is highly soluble, heat-stable, and improves growth efficiency and performance of mammalian cell culture systems. GlutaMAX™-1 eliminates problems associated with thespontaneous breakdown of L-glutamine into ammonia during incubation, allowing for longer lasting cultures. )

Importantly, glutamine binds copper while it also spontaneously breakdowns at physiological pH to ammonia which reacts with copper to precipitate light blue Cu(OH)2. This would give a partial passivation effect, making the copper surfaces less antiviral while our GlutaMAX-1 would not; hence explaining their longer time for copper inactivation.

This is one of the reasons we decided GlutaMAX-1 was the better option to avoid subsequent potential copper binding problems in the surface contact experiments.

On 2020-03-20 05:00:15, user Leo Sandip Baniya wrote:

What is the optimum temperature for COVID virus to survive ?

On 2020-03-20 14:58:48, user David C. Norris, MD wrote:

1. The pink-highlighted NEG measures in Supplementary Table 1 (see image below) would seem to be false negatives (FN), as they are followed by positive results on subsequent days. A reanalysis with these FN's imputed as POS seems indicated.

https://twitter.com/davidcn...

1. How comparable are the outside-institution RT PCR results with those from the treated group? How fragile are the apparently positive results from this study, to plausible systematic between-institution differences in test sensitivity?

On 2020-03-21 16:42:23, user Nick wrote:

I attempted to reproduce Tables 2 and 3 (R code included at the end of the post), and obtained these results:<br /> `Table 2, Day 3: reported p=0.005, calculated p=0.0136<br /> Table 2, Day 4: reported p=0.04, calculated p=0.0780<br /> Table 2, Day 5: reported p=0.006, calculated p=0.0148<br /> Table 2, Day 6: reported p=0.001, calculated p=0.0019

Table 3, Day 3: reported p=0.002, calculated p=0.0019<br /> Table 3, Day 4: reported p=0.05, calculated p=0.0429<br /> Table 3, Day 5: reported p=0.002, calculated p=0.0025<br /> Table 3, Day 6: reported p<0.001, calculated p=0.0005`

That is, Table 3 was more or less reproduced, but Table 2 wasn't; most of my p values are around twice the ones in the preprint.

Of the 8 tests, 5 produced warnings because chisq.test() doesn't like cell values of 0 or 1. Using fisher.test() from the "stats" package got rid of the warnings and caused some of the Table 2 p values to move towards the ones in the preprint, but only one (Day 6) got close. It isn't clear to me why one would use Fisher's Exact Test here --- my understanding is that it is not sufficient to invoke per-cell numbers of less than 6, as many authors seem to do, but I don't have a reference to hand for that.

Code:<br /> `t2.d3 <- chisq.test(matrix(c(10, 10, 1, 15), ncol=2))<br /> cat("Table 2, Day 3: reported p=0.005, calculated p=", sprintf("%.4f", t2.d3$p.value), "\n", sep="")

t2.d4 <- chisq.test(matrix(c(12, 8, 4, 12), ncol=2))<br /> cat("Table 2, Day 4: reported p=0.04, calculated p=", sprintf("%.4f", t2.d4$p.value), "\n", sep="")

t2.d5 <- chisq.test(matrix(c(13, 7, 3, 13), ncol=2))<br /> cat("Table 2, Day 5: reported p=0.006, calculated p=", sprintf("%.4f", t2.d5$p.value), "\n", sep="")

t2.d6 <- chisq.test(matrix(c(14, 6, 2, 14), ncol=2))<br /> cat("Table 2, Day 6: reported p=0.001, calculated p=", sprintf("%.4f", t2.d6$p.value), "\n", sep="")

t3.d3 <- chisq.test(matrix(c(1, 15, 5, 9, 5, 1), ncol=3))<br /> cat("Table 3, Day 3: reported p=0.002, calculated p=", sprintf("%.4f", t3.d3$p.value), "\n", sep="")

t3.d4 <- chisq.test(matrix(c(4, 12, 7, 7, 5, 1), ncol=3))<br /> cat("Table 3, Day 4: reported p=0.05, calculated p=", sprintf("%.4f", t3.d4$p.value), "\n", sep="")

t3.d5 <- chisq.test(matrix(c(3, 13, 7, 7, 6, 0), ncol=3))<br /> cat("Table 3, Day 5: reported p=0.002, calculated p=", sprintf("%.4f", t3.d5$p.value), "\n", sep="")

t3.d6 <- chisq.test(matrix(c(2, 14, 8, 6, 6, 0), ncol=3))<br /> cat("Table 3, Day 6: reported p<0.001, calculated p=", sprintf("%.4f", t3.d6$p.value), "\n", sep="")`

On 2020-03-21 18:05:24, user Joanna Haas wrote:

1) There were 26 patients treated with hydroxychloroquine. Of these 6 are excluded because they did not continue the full 10 day course of treatment; 3 were transferred to ICU, one died, one discontinued due to adverse reaction (nausea) and one left hospital early.

Thus among the 26 patients started on with hydroxychloroquine, 15% (4/26) went to ICU or died vs. 0/15 of the controls, a difference that may be due to chance. However the baseline characteristics of the 6 patients who deteriorated rapidly are not presented in Supplementary Table 1. The analysis of outcomes of the treated group are based on the remaining 20 treated patients.

Among the 36 patients presented in S Table I the treated group is significantly older and more have lower respiratory tract disease at baseline (30% vs 12.5%).

What is the impact of treatment on clinical course? Among the 20 patients who received hydroxychloroquine, six were given azithromycin "to prevent clinical infection". Since 5 of 6 had negative swabs at day 3, it is possible that clinical and viral status diverge.

While it is to be hoped that hydroxychoroquine with or without azythromycin will be of use in treating patients infected with SARS CoV2, the data presented in this manuscript, which is focused on viral shedding, are limited. Clinical outcome and safety data are needed. An intention to treat analysis needs to be included for the clinical outcomes.

On 2020-03-21 20:58:27, user Sinai Immunol Review Project wrote:

This study was a single-arm, open label clinical trial with 600 mg hydroxychloroquine (HCQ) in the treatment arm (n = 20). Patients who refused participation or patients from another center not treated with HCQ were included as negative controls (n = 16). Among the patients in the treatment arm, 6 received concomitant azithromycin to prevent superimposed bacterial infection. The primary endpoint was respiratory viral loads on day 6 post enrollment, measured by nasopharyngeal swab followed by real-time reverse transcription-PCR.

HCQ alone was able to significantly reduce viral loads by day 6 (n = 8/14, 57.1% complete clearance, p < 0.001); azithromycin appears to be synergistic with HCQ, as 6/6 patients receiving combined treatment had complete viral clearance (p < 0.001).

Chloroquine is thought to inhibit viral infection, including SARS-Cov-2, by increasing pH within endosomes and lysosomes, altering the biochemical conditions required for viral fusion1,2. However, chloroquine also has immuno-modulatory effects that I think may play a role. Chloroquine has been shown to increase CTLA-4 expression at the cell surface by decreasing its degradation in the endo-lysosome pathway; AP-1 traffics the cytoplasmic tail of CTLA-4 to lysosomes, but in conditions of increased pH, the protein machinery required for degradation is less functional3. As such, more CTLA-4 remains in endosomes and is trafficked back to the cell surface. It is possible that this may also contribute to patient recovery via reduction of cytokine storm, in addition to the direct anti-viral effects of HCQ.

Despite what is outlined above, this study has a number of limitations that must be considered. First, there were originally n = 26 patients in the treatment arm, with 6 lost to follow up for the following reasons: 3 transferred to ICU, 1 discharge, 1 self-discontinued treatment d/t side effects, and 1 patient expired. Total length of clinical follow up was 14 days, but the data beyond day 6 post-inclusion are not shown.

Strikingly, in supplementary table 1, results of the real-time RT-PCR are listed for the control and treatment arms from D0 – D6. However, the data are not reported in a standard way, with a mix of broadly positive or negative result delineation with Ct (cycle threshold) values, the standard output of real time PCR. It is impossible to compare what is defined as a positive value between the patients in the control and treatment arms without a standardized threshold for a positive test. Further, the starting viral loads reported at D0 in the groups receiving HCQ or HCQ + azithromycin were significantly different (ct of 25.3 vs 26.8 respectively), which could explain in part the differences observed in the response to treatment between 2 groups. Finally, patients in the control arm from outside the primary medical center in this study (Marseille) did not actually have samples tested by PCR daily. Instead, positive test results from every other day were extrapolated to mean positive results on the day before and after testing as well (Table 2, footnote a).

Taken together, the results of this study suggest that HCQ represents a promising treatment avenue for COVID-19 patients. However, the limited size of the trial, and the way in which the results were reported does not allow for other medical centers to extrapolate a positive or negative result in the treatment of their own patients with HCQ +/- azithromycin. Further larger randomized clinical trials will be required to ascertain the efficacy of HCQ +/- azithromycin in the treatment of COVID-19.

References

1. Wang, M. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research vol. 30 269–271 (2020).
2. Thomé, R., Lopes, S. C. P., Costa, F. T. M. & Verinaud, L. Chloroquine: Modes of action of an undervalued drug. Immunol. Lett. 153, 50–57 (2013).
3. Lo, B. et al. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science (80-. ). 349, 436–440 (2015).

On 2020-03-22 10:37:56, user Nathan wrote:

Here's a re-analysis based on mixed-effects logistic regressions, including time and age as covariates: https://nfaivre.netlify.com...

On 2020-03-24 15:03:38, user Sinai Immunol Review Project wrote:

Title: Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China

Summary: This single-center cohort study analyzes the clinical and laboratory features of 198 patients with confirmed COVID-19 infection in Shanghai, China and correlated these parameters with clinical disease severity, including subsequent intensive care unit (ICU) admission. 19 cases (9.5%) required ICU admission after developing respiratory failure or organ dysfunction. Age, male sex, underlying cardiovascular disease, and high symptom severity (high fever, dyspnea) were all significantly correlated with ICU admission. Additionally, ICU admission was more common in patients who presented with lymphopenia and elevated neutrophil counts, among other laboratory abnormalities. Flow cytometric analysis revealed that patients admitted to the ICU had significantly reduced circulating CD3+ T cell, CD4+ T cell, CD8+ T cell, and CD45+ leukocyte populations compared to the cohort of patients not requiring ICU admission.

Limitations: The limitations of this study include the relatively small sample size and lack of longitudinal testing. The authors also did not assess whether respiratory comorbidity – such as asthma or chronic obstructive lung disease – in addition to immunosuppression affected ICU admission likelihood.

Relevance: COVID-19 has already sickened thousands across the globe, though the severity of these infections is markedly diverse, ranging from mild symptoms to respiratory failure requiring maximal intervention. Understanding what clinical, laboratory, and immunologic factors predict the clinical course of COVID-19 infection permits frontline providers to distribute limited medical resources more effectively.

Review by Andrew Charap as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine at Mount Sinai.

On 2020-03-24 16:03:36, user Sinai Immunol Review Project wrote:

In a cohort of 222 patients, anti-SARS-CoV-2 IgM and IgG levels were analyzed during acute and convalescent phases (up to day 35) and correlated to the diseases’ severity. The same was done with neutrophil-to-lymphocyte ratio. High IgG levels and high neutrophil-to-lymphocyte ratio in convalescence were both independently associated to the severity of the disease. The simultaneous occurrence of both of these laboratory findings correlated even stronger to the diseases’ severity.<br /> Severe cases with high neutrophil-to-lymphocyte ratios had clearly higher levels of IL-6. The authors propose that a robust IgG response leads to immune-mediated tissue damage, thus explaining the worse outcome in patients with overexuberant antibody response.

A main criticism is that the criteria for stratifying patients in severe vs. non-severe are not described. The only reference related to this is the difference between the percentage of patients who needed mechanical ventilation, which was greater in patients with both high IgG levels and high neutrophil-to-lymphocyte ratio. No patient with both low IgG levels and low neutrophil-to-lymphocyte ratio was treated with mechanical ventilation.<br /> The proposed correlation of severity with IL-2 and IL-10 levels is not very strong.<br /> Furthermore, although mostly ignored in the paper’s discussion, one of the most interesting findings is that an early increase in anti-SARS-CoV-2 IgM levels also seems to correlate with severe disease. However, as only median values are shown for antibody kinetics curves, the extent of variation in acute phase cannot be assessed.

Anti-SARS-CoV-2 IgG levels and with neutrophil-to-lymphocyte ratio predict severity of COVID-19 independently of each other. An additive predictive value of both variables is noticeable. Importantly, an early-on increase in anti-SARS-CoV-2 IgM levels also seem to predict outcome.

This review was undertaken as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn school of medicine, Mount Sinai.

On 2020-03-24 19:51:57, user Aaron wrote:

From the Discussion: "Other studies have showed that high expression of ACE2 in the patients with hypertension, diabetes, and cardiovascular diseases might facilitate SARS-CoV-2 to enter the targeted cells in the respiratory system, and prolong the time of viral clearance [11, 31]."<br /> The references cited here do not show what the authors claim. Reference 11 is only a hypothesis that increased ACE2 expression in ACE inhibitor patients could lead to increased infection rates and increased case severity. These findings of ACE2 expression upregulation following ACE inhibition have only been demonstrated in rats and mice (the renin-angiotensin system is reviewed extensively in reference 31). Even if this phenomenon was shown to be identical in humans, there is no evidence showing that this upregulation leads to increased infection and/or increased case severity.

The authors go on to point out that age and incidence of hypertension, diabetes, etc. are difficult to untangle. This is a great point to make and it would be interesting if the authors can show that their cohort includes a significant population of younger patients with these comorbidities rather than the expected coincidence of older age and hypertension and/or diabetes. However, even if this is shown to be the case, an indication for hypertension or diabetes (type I or II) is not synonymous with ACE inhibitor use. Therefore, the authors should be mindful of any claims that equate hypertension or diabetes to ACE inhibitor use.

On 2020-03-26 03:45:03, user JohnMo wrote:

The inclusion of ACE inhibitors / ARB's as a covariate would also be helpful to distinguish outcomes of DM/HTN on these drugs vs. alternative drugs.

On 2020-03-26 00:03:02, user Your college professor wrote:

Some people suggest that the fact that COVID-19 binds to ACE2 receptors means there's a fertility risk involved, but we've had ACE2 binding corona viruses like HCoV-NL63 circulating for centuries and as far as I am aware nobody has ever observed any such harm from them.

We also have an autopsy of SARS fatalities, where no viral material was discovered in testicular tissues.

There's an argument to be made that the authors used an improper control group, as their control group apparently excludes men with fertility problems. The authors write:

The control group came from the population who previously received reproductive function evaluation and were classified as having normal fertility

In other words, rather than a normal distribution of the population, they're inevitably excluding a portion of subfertile men from their control group. One of the main symptoms commonly seen in subfertile men is the elevated LH levels they observed in COVID19 patients.

However, there is another problem that is more relevant than the above shortcomings. Luteinizing hormone is secreted in pulses, in a diurnal pattern. In contrast, FSH, which has no clean diurnal pattern, is not statistically significantly different between their control group and their COVID19 survivors.

What this diurnal LH pattern means is that you want to make sure that your control group is tested at the same time of day as your experimental group (ie COVID19 survivors). This explains for example why comparing different studies done on male fertility will lead to widely varying average levels of LH in different groups of subjects. The control group being measured at a different time of the day compared to the experimental group would also explain the prolactin differences seen in this particular study.

Unfortunately, the authors of this study don't mention when the control group had their values measured and when the survivors had their values measured. As a consequence, you can't consider this a proper control group, which means their results provide no evidence for their suggestion that COVID19 might cause fertility damage. Similarly, the 75th percentile they report for LH is not abnormally high, which would have been indicative of potential fertility problems.

Based on these problems, I don't see how this study would survive peer review.

On 2020-03-27 13:15:49, user Joshua Gagne wrote:

Is there an obvious explanation for why the decrease in PM2.5 would be so much larger for the other cities (18.9 ug/m3) than for Wuhan (1.4 ug/m3)? It's the opposite of my (perhaps naive) expectation.

On 2020-03-30 23:21:41, user Brian Coyle wrote:

They use Wallinga & Kretzchmar's age-based transmission matrix to model CoV2 transmission among age groups. The Wallinga estimates are based on influenza, and show "school-aged children and young adults will experience the highest incidence of infection and will contribute most to further spread of infections". This is not a useful model for CoV2, where children are not driving spread. This paper's estimates show isolating children has the biggest impact, which is almost surely not accurate.

On 2021-09-16 10:25:45, user kdrl nakle wrote:

Yup, Alberto is right, the sample is really not much to speak of. I actually tend to believe conclusions but not based on this paper. Folks, you need to do a lot more work.

On 2021-09-17 08:58:04, user Johannes Schultz wrote:

Note from the authors: This article has now been published Open Access in Schizophrenia Research: Cognition online on September 9, 2021. Here is the link: https://doi.org/10.1016/j.s...

On 2021-09-17 16:27:49, user Daniel Keyes wrote:

I commented previously that the apparently long delay in peer review is understandable, and typical for many journals. However, given the extremely high profile of this article, it should have been considered for expedited review. Now even "regular" review seems to be taking rather long. This could be due to reviewer delay, reviewers or editors requiring a large number of changes, or it may even reflect a general reluctance to publish an article with this conclusion.

On 2021-09-17 17:39:54, user Gabriel Lee wrote:

I do not understand the numbers for vaccine doses administered during the June 1 to July 31 period. These seem far too low for a city with a population of almost 1 million and the two-month period during which some of the fastest vaccination rates in Ontario and Canada were recorded. I downloaded the CSV file from open.ottawa.ca and tallied the Moderna and Pfizer-BioNTech doses in this period, and found 352,687 and 481,264 doses, respectively. Could you please explain?

On 2021-09-22 17:13:20, user dansari wrote:

The authors do not describe their methodology for comparing incidence of myocarditis/pericarditis to background rates, and thus whether they have been disproportionately reported following vaccination, nor whether this comparison has indeed been performed. Reference (8) does include this detection.

As mentioned in other comments, the "Vaccinated in Ottawa" data (is this the dataset that was used?) indicate that 838,442 vaccinations were given during the time frame of this study. This would yield approximately 4 cases per 100,000, a figure more in line with currently understood vaccine statistics.

On 2021-09-25 19:07:25, user Peter Dimitrov wrote:

Time frame : 60 days following vaccination; Location: who presented at a single academic institution/Ottawa Heart Centre. Patients were identified by admission and discharge records of the Ottawa Heart Centre. Sample size: 32 patients, 29 of which were male! Median time between vaccination dose and pain symptoms was 1.5 days. Startling findings by themselves, ought to raise curious questions not outright dismissal/withdrawal.

However, obviously the incidence rate based on total MRna vaccines in Ottawa area is waay off. Am curious to know disaggregated sex/age etc data of Myo/peri cases recorded in the exact same time period in all the other hospital treatment centres in Ottawa area?

On 2021-09-21 14:02:09, user Isatou Sarr wrote:

If it works, why not!!!!! What is the genome similarity index between MEASLES-MUMPS-RUBELLA (MMR) and COVID-19? Is there any common clinical manifestation identifiers between the ailments?

On 2021-09-25 09:47:21, user Jan Podhajsky wrote:

Hi there. There is a question about personal and sensitive data protection during obtaining answers via questionnaire distributed through social web.

1. Unsufficient introduction to the survey. No mention about sensitive data personal data being colellected via questionnaire in consent question
2. Missing contact to authority responsible for Personal and sensitive data protection
3. Doubts about processing of personal data especially electronic personal data like cookies, refferals, geolocation
4. Questionnaire enabled continuation without previous login into the system which might lead to other person to access personal and sensitive data, e.g. on shared computers

I raised these concerns to data protection authority of Faculty of Scince, CUNI.

The questionnaire research did not met personal and senstive data protection standards. It is unethical research by my opinion.

On 2021-09-25 12:55:23, user Raja Mugasimangalam wrote:

Excellent.<br /> The title of the article can be compressed a bit.

On 2021-09-27 18:07:42, user DiogenesNJ wrote:

"early attention directed towards identifying SARS-CoV-2 in returning <br /> international travelers may have led to a failure to recognize locally<br /> circulating infections..."

And why were we limited to that? A shortage of testing capability attributable to CDC's insistence on their own test, which turned out to be flawed, and FDA's refusal to allow any of several other tests developed by the private sector or universities to be used during the crucial first months of the pandemic. A classic NIH problem (Not Invented Here, not to be confused with the National Institutes of Health).

Compare and contrast with South Korea, which called in every big pharma company in the country during their New Year holiday, approved a private-sector test in early February, and had massive testing up and running in less than a month (15k tests/day capacity by the end of February).

On 2021-09-30 02:46:32, user Fiona Weir wrote:

70% of people in Dane County are vaccinated [6-your source]. If representative, you would expect a similar profile in your study; however only 38% of your cohort is vaccinated. This raises crucial questions about selection/inclusion... Was self-reporting reliable? Were cases excluded when vaccination status was not self-reported? Were unvaccinated people much more likely to test? Were vaccinated people likely to test only if they were actually ill, and therefore likely to have a higher virus load in any case? These issues plus the low cohort size may make your findings unreliable.

On 2021-09-30 12:14:12, user Joren Buekers wrote:

Exciting research! I hugely support focussing on continuous SpO2 measurements instead of discrete/spot check measurements only! I'm happy that this finally found its way to COVID research. <br /> A small remark/request: you indicated that "preprocessing of the raw SpO2 signal was performed using a block filter as in Levy et al.", but this block filter was actually developed in another study (https://doi.org/10.2196/12866) "https://doi.org/10.2196/12866)"). Would it be possible to acknowledge the original paper as well? (Sorry for the self-promotion, but I do think it's more correct to refer to the original paper).

On 2021-10-11 05:16:51, user Jonathan Sobel wrote:

Dear Dr Buekers,<br /> Thanks a lot for your interest in our work and your supportive comment. Your work is indeed inspiring and we will cite it in a revised version of our manuscript.<br /> Best Regards,

On 2021-09-30 20:18:12, user Navneet Dhillon wrote:

This article is now published in Journal of Extracellular Vesicles 2021;10:e12117, <br /> “Extracellular vesicle-mediated endothelial apoptosis and EV-associated proteins correlate with COVID-19 disease severity” PMID: 34262673

https://doi.org/10.1002/jev...

On 2021-10-01 13:49:12, user Jasper wrote:

I'm wondering if there's any research on the long term effect of the single-shots. Most studies have antibodies, B and T cell checks at one week after the second dose. Doesn't that result interfere with a possible prolonged effect of the first dose? This study shows that there's a sound immune response, that apparently (according to the BNT162b2 clinical studies) provides ample protection 12 days after the first dose (especially if you don't take into account the positive cases during the first 12 days without protection). VE also seems really good in real-life - albeit the time period and groups are smaller - but still massive, considering the magnitude of this operation. Maybe we don't need to boost with 0,3ml, and so on.

On 2022-01-19 14:21:14, user jhnnaso wrote:

This study is now published here: https://bmcmedicine.biomedc...

On 2021-10-01 15:08:14, user Vince Dhimos wrote:

The developers should now do a comparative study with other competing vaccines.

On 2021-10-03 18:28:32, user Joseph Psotka wrote:

It would be much more useful to look ar discrepancies in the immune system of the twins. Even dizygotic twins can have the same immune system.

On 2021-10-04 07:26:13, user Wolfgang Wagner wrote:

Int J Mol Sci. 2021 Aug 27;22(17):9306.<br /> Epigenetic Clocks Are Not Accelerated in COVID-19 Patients

PMID: 34502212 <br /> PMCID: PMC8431654 <br /> DOI: 10.3390/ijms22179306

On 2021-10-05 09:40:08, user leecanning123 wrote:

A major issue is that the pcr test is being used in this study, it is well known pcr produces false positives and as such any one of the placebo cases could be illness that is not connected to sarscov2, much like millions of "cases" around the world over the last 20 months. The FDAs own document stated that early pcr was based on "contrived" samples, meaning, not even real sarscov2.

On 2021-10-06 06:00:28, user Stuart wrote:

Could the incorporation of altered nucleosides into the viral RNA affect the ability of the reverse transcriptase in the RT-PCR reaction from actually detecting the viral RNA, even if it is there? Can they verify the results using antigen tests instead?

On 2021-10-10 05:14:46, user kdrl nakle wrote:

Needs to point out that this is all prior to Delta and that changes everything.

On 2021-10-11 16:09:28, user sentner wrote:

I'm surprised this article is still in a pre-print state. It's a hot topic and it's now been available for 6 weeks, which is plenty of time for peer review. Usually by now it's either rejected or accepted for wide publication in peer reviewed journals. It makes me wonder if, due to the politicization of this topic, some scientists are deciding not to review this document at all in a fair way.

On 2021-10-14 14:17:58, user Julian von Mendel wrote:

This paper has now been peer-reviewed and published, with no substantial revisions: https://www.mdpi.com/1311862

Citation:<br /> Borsche, L.; Glauner, B.; Mendel, J.v. COVID-19 Mortality Risk <br /> Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close <br /> to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis. Nutrients 2021, 13, 3596. https://doi.org/10.3390/nu1...

On 2021-10-14 19:09:32, user Dave Green wrote:

This trial was listed as one of the clinical trials being done on Ivermectin on the FDA website. The media has portrayed the use of this drug as completely ridiculous and idiotic. Yet, there are several clinical trials underway to prove or disprove its effectiveness. If its use is so "idiotic" then why would highly educated people bother to study it???

This is an example of one (of several) that shows it is effective and has promise. From what I have read this "effectiveness" increases if it is given early on. Where I live in Canada, if you have symptoms you are just told to self isolate until they become so bad you have to be hospitalized. You are not provided Vitamin D, Zinc, Ivermectin or any other form of treatment that could help prevent you from being hospitalized. Everyone criticizes any study that comes out and nothing can be proven or believed. It is so frustrating.

Thank-you to the people who performed this study. Your efforts to help the world are appreciated, if not by everyone, at least by me.

On 2021-10-10 19:52:00, user Markus Falk wrote:

The study seems well performed. However, although randomized, result may be related to different starting values. It seems that the placebo group had a marginally higher viral load at beginning. A Wilcoxon-test for the matched pairs of day 0 and 6 may give some insights. Decrease of viral load from day 0 to 6 seems to be paralleled and only offset by starting values. Adding starting values to the logistic regression may correct for this.

On 2021-10-18 20:32:04, user Immede wrote:

Nice, the city of Wuhan is actually out of the zone indicated on their probabilistic maps.

On 2021-10-25 19:36:50, user Henry wrote:

Could these studies possibly be construed as gain of function?

On 2021-11-01 14:33:28, user happydog wrote:

This article has now been accepted for publication in Epidemiology & Infection (https://www.cambridge.org/c... "https://www.cambridge.org/core/journals/epidemiology-and-infection)").

On 2021-11-05 19:55:40, user Mazen Baroudi wrote:

Now published by BMJ Open

On 2021-11-09 23:59:36, user Jessica Grevis wrote:

Very interesting article. I'm curious if there is information on more specific professions, like an extended Table 2. I'm particularly interested in the construction trades.

On 2022-11-06 18:39:10, user Knut M. Wittkowski wrote:

A peer-reviewed version of this pre-print has been published as https://doi.org/10.7759/cur...

On 2022-12-08 22:41:55, user Dr. Kate wrote:

It's interesting to see what has become of this paper after peer review. A lot of the conclusions that made it on the front pages in German media are now significantly toned down. It should be a warning to all of us how quickly media jump on certain conclusions that are popular at the time, even if they do not hold up to scientific scrutiny. Also, neither media nor public opinion tend to look back and check which part of the initial report held up to peer review and which ones had to be significantly reworked.

On 2023-11-08 17:24:49, user Paul Auer wrote:

Great paper. Very interesting work. One question about calculating dilution across multiple studies. Suppose one study used say the 1000 Genomes reference panel for imputation and another study used the TOPMed reference panel for imputation. If we compare the summary statistics between these two studies, might we see systematic differences in effect sizes if the imputation quality is quite different? i.e., might differences in imputation be confounded with phenotypic misclassification as estimated by PheMED?

On 2022-01-09 23:14:33, user Neil Bogdanoff wrote:

So why no mention about how people can test positive with both antigen and PCR tests for Covid-19 for up to three months after infection? And how might that portion of the population impact the results of the study? Also, is there some analysis as to why the different type of vaccines might play a role? And of the population studied, which vaccines did they receive--and what percentage had received booster shots? When will the study be peer-reviewed?

On 2022-01-13 08:19:03, user PierreLouis wrote:

Nice study. I disagree with your conclusion, though. We can’t deduce from the data that dogs sensed persistance of viral infection. They may sense the smell associated with the so-called long Covid syndrome. Which may not related to viral persistance but to post-infection metabolic chronic disturbance. Interesting controls would be patients with non infection-related depression and patients with chronic fatigue after another infection (cured bacterial sepsis for example). Anyway, a very original and provocative study!

On 2022-01-14 03:44:42, user Mike B wrote:

Although your result shows that analytical sensitivity is similar for both variants, more critically it also echos by analytical evaluation (" 5 of 11 (45%) Omicron samples were negative despite having levels of virus above the LoD." ) the numerous clinical complaints that significant false negative results suggest that this test is unreliable as a screening tool to identify infected and contagious individuals or as a negative screening tool via serial testing in a specific populations. (travel, school, theatre arts, music, live performance). This study is significant because it's sample set comes from asymptomatic and almost entirely fully vaccinated donors. <br /> There is good concordance with a recent clinical study (Adamson, Sikka, https://doi.org/10.1101/202... ). In that study they confirm infectious transmission on day 1, with day 0 being Limit of Detection via RT-qPCR. In their study antigen tests did not turn positive until day 3 with viral loads via RT-qPCR somewhat lower than days 1 and 2. This study confirms a false negative issue and eliminates sampling technique as the source because RT-qPCR was run from the same sample as the antigen test. The clinical significance of this issue is of primary importance in context of the rapid rise in viral load and infectious transmission of Omicron as highlighted in the clinical study. The cause of the false negative issue needs urgent exploration. Thanks for a great job and continued hard work. Valuable information.

On 2022-01-14 21:44:55, user JJ wrote:

The results are interesting and valid - but in my opinion, this is true only until the moment when the testing strategy started to differ for vaccinated and unvaccinated individuals (since about the end of summer 2021, vaccinated individuals did not have to test even if in close contact with a PCR-positive person while unvaccinated had to do so). This naturally lead to the increased difference between the numbers of unvaccinated than vaccinated PCR-positive individuals, which is a major source of bias that should be, in my opinion, removed.

On 2022-01-17 00:08:52, user Satvinder Singh Bawa wrote:

The key findings of this study are identical to the South California study. Vaccines are effective for Delta. Not for Omicron. Infection rates are actually highest in the boosted. But hospitalizations are lowest in boosted.<br /> https://www.medrxiv.org/con...

On 2022-01-18 15:04:19, user JJackson wrote:

Figure 1a shows about a 10 day difference between the onset dates for delta and omicron cases with delta averaging mid Dec and Omicron nearer Christmas. Given that the date on the paper is 11th Jan this just is not giving adequate time for disease progression in the Omicron cases to expect ICU admissions and deaths. For a fair comparison numbers of hospitalisation, ICU admissions and deaths for Omicron should be take 10 days later than for Delta.

On 2022-01-18 23:47:58, user Alexander Novokhodko wrote:

Was this patient vaccinated?

On 2022-01-29 14:34:02, user Alberto wrote:

Thank you for highlighting this problem. It's amazing that indoor air quality has been so ignored apart from some "open the windows" advise.

On 2021-10-17 02:07:31, user X Basch wrote:

Xu, Katherine et al. “Elevated NGAL is Associated with the Severity of Kidney Injury and Poor Prognosis of Patients with COVID-19.” Kidney international reports, 10.1016/j.ekir.2021.09.005. 8 Oct. 2021, doi:10.1016/j.ekir.2021.09.005

On 2022-02-01 02:14:51, user Sulev Koks wrote:

The manuscript has been accepted for publication in Experimental Biology and Medicine.

On 2022-02-03 22:33:14, user Maksim wrote:

The manuscript is now accepted for publication <br /> ( Coronaviruses, Bentham Science) <br /> https://www.eurekaselect.co...

On 2022-02-08 01:31:14, user Nils S wrote:

If it was true that unvaccinated had so little protection against Delta as you indicate, Delta would not have disappeared. <br /> Obviously, reality confirms that immunity of an Omicron infection is much broader than your analysis shows. <br /> Think about T cells, IgA, mucosal immunity…

On 2022-02-08 08:06:00, user kdrl nakle wrote:

Plus of course large portion of population gets annual vaccination for Influenza so there is no such drama about future flu as some would like us believe. But we better prepare for H5 coming.

On 2022-02-26 15:01:29, user Rogerblack wrote:

The paper investigates symptoms remaining after 12 weeks. 15 weeks ago, 11M/46M of the UK population was boosted. (3 weeks for immune response and paperwork)

While perhaps smaller numbers than we might like, this would lead to approximately 63 (294(2-dose)*0.22) boosted in your cohort developing LC, if there is no change in risk from doubly vaxxed.<br /> This is not good enough to show if the protection from LC is slightly increased, but it is certainly enough to exclude an OR of (say) 0.1 or 0.2, which would be valulable to report.

It is my understanding that the CIS also contains questions related to employment/role.

What fraction of those reporting activity limitations have had changes on those metrics?<br /> An impatient advocate.

On 2022-02-27 04:15:03, user RonG wrote:

Dr. Bredesen most certainly does have a "conflict of interest". He uses this article to promote his company and sales of his "bestselling" book. For me, this lack of transparency casts grave suspicion on the results. Many scientists and doctors work with corporations to publish research, but they honestly acknowledge that association.

On 2022-03-25 20:53:31, user kpfleger wrote:

I didn't notice mention of the date range over which events were considered (did I miss it?). We know it takes time (many weeks) for 25(OH)D to rise after initiation or increase in oral daily D3 intake. A jump from zero to 800 IU/d will reach steady state relatively quickly, but a jump from 0 to 3200 will take maybe a month to reach 1/2 to 2/3 of the way to the new steady state 25(OH)D and ~2 months get most of the rest of the way. See for example Fig 1 (looking at the 125ug line) of "Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol" Heaney et al 2003:<br /> https://academic.oup.com/aj...

A well enough funded study could have done interim 25(OH)D tests, but I realize that was not possible here. Without such tests, if analysis for the 3200 vs no-offer was not limited to the range of dates for which the 3200 offer arm should reasonably have been expected to have fully increased their serum levels, then any effect may have been significantly diluted (due to mixing in infections in the offer arm(s) before the supplements could have done much good).

To the extent to which vaccination over the course of the 6 months of the trial caused a drop in infection events as each subject became vaccinated, that could have exacerbated the dilution by leaving fewer months between achievement of new raised 25(OH)D levels and increased protection from vaccination. How many of the infection events happened if the final 1-2 months?

I hope this issue can be addressed before publication. It would be interesting to see a graph with the full 6 months of the trial on the x-axis and number of infections per week for each of the 3 arms plus some measure of the cumulative % of each arm vaccinated by that point in time.

On 2022-03-27 12:21:47, user helgarhein wrote:

To bring my immune system into best working order I would want to be vitamin D replete for some months or years. (Similar to the finding that it took 5 years of 2000 IU daily to reduce the incidence of auto-immune diseases, Hahn et al BMJ, Jan 2022.) This trial lasted only 6 months, but, crucially, we are not told when the optimal blood level was reached. Only once the optimal level for immune health has been reached should an assessment happen. This is 75 nmol/l. Some individuals might need more than 3200 IU to reach it, some might even reach it in the 800 IU group. Could this subgroup be assessed: Those who achieved the defined sufficient 25(OH)D level across all 3 groups? Did this ‘replete’ group have reduced incidence of Covid infections?

On 2021-11-02 11:31:33, user Tom Jefferson wrote:

The review has now been published in Clinical Microbiology and Infection: https://doi.org/10.1016/j.c...

On 2022-05-12 03:50:58, user Stuart wrote:

Published in JCI Insight here: https://insight.jci.org/art...

On 2021-11-14 16:21:34, user Isaac Núñez wrote:

This article has been published in the journal 'Medicina Intensiva' and is available at the following URL: https://www.sciencedirect.c...

On 2021-11-15 16:28:10, user kdrl nakle wrote:

None of this is surprising and it has more to do with socio economic status than anything else.

On 2022-07-12 03:17:06, user Souradeep Chowdhury wrote:

The article has been accepted for publication; please find the link attached:

https://pubmed.ncbi.nlm.nih...

Please review and link to the published version. Regards

On 2025-02-15 00:44:43, user HLA.Fan wrote:

The authors should not make up nomenclatures for discussing HLA alleles. "HLA-DQB1*57" is not a valid way of describing variation at amino acid position 57 of the DQB1 gene. Similarly, "DRB1*13", confuses the appropriate 1-field descriptor for all DRB1*13 alleles with variation at amino acid position 13 of the DRB1 gene. No where in this preprint do the actual amino-acid variants seem to be discussed.

Further, the authors refer to "two- and four-digit HLA alleles". The digit-based HLA nomenclature has not been in use for almost 15 years (see: DOI: 10.1111/j.1399-0039.2010.01466.x). The authors should familiarize themselves with and use, modern, field-based HLA nomenclature.

Finally, when the authors do use HLA allele names, the names must be used consistently. When one is referring to an allelic HLA gene variant, the entire allele name is italicized. When one is referring to a specific HLA protein variant, the allele name is not italicized. There is no situation in which, e.g., "HLA-DQB1" should be italicized when "*02:01" is not italicized.

On 2022-01-30 16:41:48, user Mary Beth Baker wrote:

Am a non-medical, non-math lay person, but in the comparison with the influenza pandemic of 1918/1919, it says that 1/4 of the US population was infected whereas 1/5 has been infected with Covid-19. Doesn't that make influenza worse, so far anyway? 6 in every 1,000 died of the spanish flu in US. How many per 1,000 of Covid so far?

On 2022-02-05 13:03:59, user GregoryGG wrote:

Hello,<br /> Unless I misunderstood, <br /> How do you know that the behaviour of people, the transmission prevention measures and the testing entry rules were the same between delta and omicron; and between vaccinated and unvaccinated ?

Also, since we know that immunity against a single variant may lower down over time, can we still consider single- and double-dosed people as being vaccinated? (they could be considered as non vaccinated over time).

Thank you.

On 2022-02-09 20:37:04, user anon wrote:

This is completely nonsensical after a population wide study by Patone et al. showed the pooled risk of developing myocarditis to be higher after any mrna vaccine series compared to covid infection for males <40. Yet 1000x higher from covid? I have to say, even among covid long hauler communities, compared to communities with vaccine side effects, the prevalence is much higher in the vaccine communities. Where am I missing the extra 1000 people for every extra person in the vaccine communities?

On 2022-02-16 16:01:22, user Matthias Bruhn wrote:

The ELISAs in Fig. 1 are saturated at OD 3.0, this “swallows” any differences between the variants. The conclusion that vaccinated + omicron infected makes antibodies equally strong against all variants should not be drawn based on saturated measurements

On 2022-02-21 12:44:14, user Amador Goodridge wrote:

This work have been complemente with a video reagarding all findings. Please see authors explaning the research here https://youtu.be/Z2X306wc-JU

On 2025-11-30 16:49:17, user Cyril Burke wrote:

[Note: This is the first of several reviews of an earlier version of our combined manuscript that aims to reduce ‘racial’ disparity in kidney disease. The comments were kindly offered by nephrologists, through a medical journal, and we remain grateful to them for the time and care they gave to improve our manuscript.

We removed identifying features and will include our responses in a subsequent comment. The changing title and line numbers refer to versions prior to our medRxiv preprints.]

April 1, 2022<br /> Screening for early kidney disease and population health using longitudinal serum creatinine

Dear Dr. Burke III,

REDACTED.

Reviewer #1: Burke et al submit a somewhat unusual paper, devoted to a topic of potential major clinical relevance, and as yet understudied.

General comments

1. The thesis of the authors, that using the baseline serum creatinine of a given patient would potentially improve the earlier diagnosis of kidney disease, even in the normal range, is in line with the experience of this reviewer, who always retrieves , whatever the difficulty of reaching that goal, past results of blood tests, and uses them as a way to date the onset of kidney disease, sometimes with important prognostic implications.

2. Yet, the authors do not provide data strongly supporting their thesis. For instance, when looking at case 2, should the last point (the most recent one) be omitted, there would be very little evidence supporting progressive early kidney disease.

3. The claim that the statistics fit the data better when all points are used (page 9,11) should not come as a surprise. Using thresholds instead of the full range of values has long been known to be more powerful for statistical analysis. But fitting the data does not equal to a high positive predictive value!

4. A key question is whether in a real world context, the earlier diagnosis of kidney disease would be possible, without too much background noise from intercurrent illness (functional), drugs (NSAIDS, etc..). In other words, would the specificity (or PPV) of the suspicion of early kidney disease be reasonable enough to catch the attention of clinicians

5. Even though there has been improvement in the standardization of measurement of serum creatinine (IDMS), the comparability of results measured by different labs remains suboptimal, at least in the experience of this reviewer, and medical shopping is not uncommon, making the availability of all previous results in the same graph a logistical challenge.

Specific comments

1. The authors should mention that the USPTFS decided a month ago to revisit the question of screening for kidney disease in high risk groups (page …)

2. Even though ESRD has a legal meaning in the USA, not very relevant to the topic of this paper about early kidney disease, the authors should stick to the nomenclature proposed by a recent KDIGO consensus conference (see Levey et al. Nature Reviews in Nephrology ). In particular, use kidney failure instead of ESRD/ESKD. When the topic is glomerular filtration, use that wording instead of kidney function (page…)

3. The authors allude to the concepts of prediabetes and prehypertension. But this reviewer points to the fact that the levels used to define those entities are currently “generic” , rather than based on previous values in an individual subject. Please discuss.

4. The authors repeatedly mention in the discussion section evidence that even small increases in serum creatinine have prognostic significance. This has indeed been known for decades but is a different topic: AKI . Admittedly, there is growing evidence that AKI and CKD are linked. But that the stability of a biological parameter is prognostically best is all except surprising: the same is true for body weight, mood, blood pressure etc…

Reviewer #2: Thank-you for the opportunity to review this work which highlights the importance of monitoring serum creatinine over time and how this can be a useful tool in detecting possible CKD. This is an important topic as the use of sCr on its own is certainly under-utilised and changes are often missed because they don’t fall into a predefined category.

MAJOR CONCERNS

“Choi- rates of ESRD in Black and White Veterans” doesn’t fit with the rest of the paper including the title; the introduction and conclusion also don’t adequately address this portion of the paper. It feels disjointed from the main point of discussion which is the use of sCr in screening “pre-CKD”. This section and discussion should be removed and possibly considered for another type of publication.

Cases 1 - 3, (lines 93 – 122): where are these cases from? There is no mention of ethics to publish these patient results, which appears to be a clear ethics violation. If so, these cases should be removed and patient consent and ethical approval obtained to publish them.<br /> The authors describe the reasons for not obtaining an ethics waiver for this secondary data analysis. Despite this, the relative ease of obtaining an ethics waiver for secondary data analysis usually means that this is done regardless.

The message of the article and data representation is unclear: do the authors wish to show that sCr is superior to eGFR in this “pre-CKD” stage, should both be used together? Do the authors wish to convey that a “creatinine blind range” does not exist? Or is the aim to demonstrate that continuous variables should not be interpreted in a categorical manner?

MINOR CONCERNS

ABSTRACT<br /> Vague<br /> Doesn’t give a clear picture of the study

INTRODUCTION<br /> 51 – 57: needs to state that these stats are from e.g. the US. The authors should consider adding international statistics to complement those from the US.

68: reference KDIGO guidelines, state year

75 – 77: is this reference of the New York Times the most appropriate?

82: within-individual variation not changes (this is repetition of the point made in lines 425 – 427, but should match the language)

82 – 84: reference? If this is a question it should be presented as such

84: “normal GFR above 60” = guidelines (including KDIGO) do not refer to 60 as normal GFR, 60 – 89 is mildly decreased. (see line 126)

93: avoid the use of emotive words such as apparently (also in line 428)

94: “Not meeting KDIGO guidelines”: KDIGO 2.1.3 includes a drop in category (including those with GFR >90). This would appear to include some of the cases listed. Additionally, albuminuria should have been measured for case 2 and 3.

97: “progressive loss of nephrons equivalent to one kidney”: this is based on a single creatinine measurement.

93 – 122: Could any of these shifts be explained by changes in creatinine methodology or standardisation of assays, especially over 15 – 20 years (major differences between assays existed before standardisation and arguably still exist with certain methods).<br /> It would be useful to see a comparison between serial sCr and eGFR measurements on the same figure. There appears to be significant (possibly more pronounced) changes when eGFR is used. As line 87 mentions changes in eGFR may be as useful (and in some situations more useful) than changes in sCr alone.

127 – 142: should there be separate charts for males and females, the differences in creatinine between males and females needs to be discussed somewhere in the paper. Similarly, is this suitable for all ages?

162 – 163: rephrase

METHODS<br /> 185 – 193: aim belongs in the introduction, can be adjusted to complement paragraph 178 – 182.

196 – 205: reference sources

224 – 247: not in keeping with the rest of the article or title and conclusion

RESULTS<br /> If eGFR is treated as a continuous variable does inverted sCr still have higher accuracy?

As mentioned, the section on ESRD in black and white veterans doesn’t fit in with the rest of the article.

DISCUSSION<br /> As mentioned, section 4.1 doesn’t fit in with the rest of the article. As the authors note the correlation between illiteracy and CKD is likely not causal.

387: erroneous creatinine blind range. The data presented does not show this is erroneous there is still a relative blind range. A distinction must be made between a population level “blind range” and an individual patient’s serial results. The data and figure 4 in particular demonstrate the lack of predictive ability of sCr above 40ml/min compared to below 40ml/min at a population level. For an individual patient this “blind range” is more relative, and a change in sCr even within the normal range may be predictive. (Note: the terminology “blind range” is problematic).

399 – 400: “rose slowly at first and then more rapidly as mGFR decreased below 60” this refers to a relative blind range. Whether these slow initial changes can be distinguished from analytical and intra-individual variation is the question that needs to be answered before we can say a “blind-range” doesn’t exist for an individual patient.

425 - 432: sCr is indeed very useful when baseline measurements are available. eGFR remains useful when baseline sCr is not available or when large intervals between measurements are found.

425: low analytical variation- if enzymatic methods are used

428: avoid the use of “apparently”

430: reference 56 compares sCr and sCysC with creatinine clearance NOT with mGFR, this does not prove that mGFR has greater physiologic variability. Creatinine clearance is known to be highly variable (partially due to two sources of variability in the measurements of creatinine: serum and urine).

The limitations of sCr for screening should also be discussed: differences in performance and acceptability between enzymatic and Jaffe methods (still widely used in certain parts of the world), the effect of standardizing creatinine assays (an important initiative but one that could also produce shifts in results around the time of standardization- see cases), low InIx means that once-off values are exceedingly difficult to interpret, is a single raised creatinine value predictive (or should there be evidence of chronicity): similarly are there effects from protein rich meals, etc (The influence of a cooked-meat meal on estimated glomerular filtration rate. Annals of Clinical Biochemistry. 2007;44(1):35-42. doi:10.1258/000456307779595995)

CONCLUSION<br /> The discussion recommends using SCr above eGFR while the conclusion recommends the NKF-ASN eGFR for use in pre-CKD and ASC charts. While the use of both together in a complementary fashion is understandable- this needs to be congruent with the discussion, aims and results.

On 2022-03-05 07:28:21, user Kaiser Stobbertus wrote:

A good study!<br /> I just wonder, though, why PEM (Post-Exertional Malaise) was not taken into account - especially given the expectable long-term suffering in patients who might get prescribed excercise?<br /> On topic, see, e.g.:<br /> https://www.ncbi.nlm.nih.go...

On 2020-04-20 17:17:34, user Andy wrote:

On the self-selection, non-random bias, participants were asked about "prior clinical symptoms".

But even that is not enough to correct the bias. People are more likely to participate if they think they have been exposed, not just because they had symptoms.

So the result is still going to be wrong after accounting for "prior clinical symptoms", because participants were self-selected for exposure.

On 2022-04-20 20:37:11, user Mark Czeisler wrote:

Note from the authors:

This paper was published in Sleep Health on 20 April 2022 following peer review. Below is a link to the article.

DOI: https://dx.doi.org/10.1016/...

Mark É Czeisler, Emily R Capodilupo, Matthew D Weaver, Charles A Czeisler, Mark E Howard, Shantha MW Rajaratnam. “Prior sleep-wake behaviors are associated with mental health outcomes during the COVID-19 pandemic among adult users of a wearable device in the United States.” Sleep Health. 2022. DOI: 10.1016/j.sleh.2022.03.001

On 2022-05-22 17:15:49, user Teresa Moreno wrote:

UPDATE MAY 2022: lessons for the monkeypox viral outbreak?

According to the Johns Hopkins data repository (updated in Dong et al 2020), case numbers of COVID-19 in Spain rose steadily and rapidly after the early December 2021 holiday to an omicron-driven post-Christmas peak far higher than any other during the SARS-CoV-2 pandemic. On 8th December 26,412 new cases were recorded, whereas by 11th January 2022 this figure had risen an order of magnitude to 292,394. The entirely predictable threat of a countrywide viral superspreading event boosted by Christmas celebrations, many in poorly ventilated indoor environments, had become real, with deaths from the disease peaking in late February 2022.

In May 2022 cases of monkeypox suddenly emerged in several countries worldwide. The pathogen responsible for this enzootic disease is belongs to the Orthopoxvirus genus which includes the virus causing smallpox. How is this global outbreak of monkeypox being transmitted? As in the early days of the emergence of COVID-19, initial public health statements are emphasising personal hygiene and avoidance of close physical contact with the saliva or lesions of infected individuals (ECDC 2022; Koslov 2022). The World Health Organisation states that "monkeypox virus is transmitted from one person to another by close contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding" (WHO 2022). This initial reaction to a new pattern of infectious disease is familiar (Moreno and Gibbons 2021). The spread of the now-eradicated smallpox virus was similarly considered to have been transmitted primarily by fomites and close contact, until the classic nosocomial outbreak in the German town of Meschede. Study of this event concluded that cases spread inside the hospital were infected by virus particles disseminated by air over a considerable distance (Wehrle et al., 1970, see also Gelfand and Posch 1971; Fenner et al., 1988; Tellier et al., 2019). Reviewing the history of this disease, Milton (2012) concluded that "the weight of evidence suggests that fine particle aerosols were the most frequent and effective mode of smallpox transmission". Given our precautionary recent experience and slow start with SARS-CoV-2, we argue that we should be treating this unexpected new zoonotic poxvirus outbreak as likely being driven at least in part by viraerosol transmission. It is another wakeup call for treating indoor air ventilation issues more seriously.

References<br /> Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020 May;20(5):533-534. doi: 10.1016/S1473-3099(20)30120-1. Epub 2020 Feb 19. Erratum in: Lancet Infect Dis. 2020 Sep;20(9):e215. PMID: 32087114; PMCID: PMC7159018.<br /> European Centre for Disease prevention and Control. Epidemiological update: Monkeypox outbreak. 20 May 2022. <br /> Fenner, F., D.A. Henderson, I. Arita, Z. Jezek, I.D. Ladnyi. Smallpox and its eradication. WHO, Geneva (1988), p. 1460p<br /> Gelfand, H.M., J. Posch. The recent outbreak of smallpox in Meschede. West Germany. Am. J. Epidemiol., 93 (4) (1971), pp. 234-340, 10.1093/oxfordjournals.aje.a121251<br /> Moreno, T., Gibbons, W. 2021. Aerosol transmission of human pathogens: From miasmata to modern viral pandemics and their preservation potential in the Anthropocene record. Geoscience Frontiers. DOI:10.1016/j.gsf.2021.101282<br /> Kozlov, M. 2022: https://www.nature.com/arti... "https://www.nature.com/articles/d41586-022-01421-8)")<br /> Milton, D.K.. What was the primary mode of smallpox transmission? Implications for biodefense. Front. Cell Infect. Microbiol, 2 (2012), p. 150, 10.3389/fcimb.2012.00150<br /> Tellier, R. Aerosol transmission of influenza A virus: a review of new studies. J. R. Soc. Interface, 6 (2009), pp. S783-S790, 10.1098/rsif.2009.0302.focus<br /> Wehrle, P.F., J. Posch, K.H. Richter, D.A. Henderson. An airborne outbreak of smallpox in a German hospital and its significance with respect to other recent outbreaks in Europe. Bull. World Health Organ., 43 (5) (1970), pp. 669-679<br /> World Health Organisation. Multi-country monkeypox outbreak in non-endemic countries. May 21 2022. https

On 2022-05-23 11:58:04, user Jakub Fronczek, MD wrote:

Brilliant paper, congratulations - great to see net benefit assessment. The only part I found confusing is: "In sub-2% decision thresholds there is no net benefit in using our system, but these patients are not a subject of interest in this analysis and should always undergo a biopsy". Since the analysis includes BI-RADS 4 patients, shouldn't a probability <2% be of interest as a criterion for downgrading a patient to a lower risk category? Perhaps I'm missing something! Kind regards, Jakub Fronczek.

On 2022-06-03 09:49:21, user Rodger Moore wrote:

Dear author et al. This statistical research under a population of 800.000 suggests a different conclusion. https://www.mdpi.com/2077-0...

On 2022-06-10 21:11:43, user Won-Seok Kim wrote:

This manuscript was published online in European Journal of Vascular & Endovascular Surgery. DOI: 10.1016/j.ejvs.2022.05.047

On 2022-06-13 15:40:35, user Myia Mcmillian wrote:

While an interesting study, I would be very curious about the number of subjects involved who were truly Covid-naive. The CDC claims that only 1 in 4 Covid infections are reported: https://www.cdc.gov/coronav..., and by the time of the Omicron wave, supposedly producing breakthrough infections in both vaccinated and previously Covid-infected, most Americans had likely been infected with Covid at least once. Does that confound the study?<br /> Additionally the median age of death from Covid is >80 years old, and most serious cases are in the Elderly and seriously ill. Younger people generally fight off Covid, variably.<br /> As the Danish researchers recently showed in a re-evaluation of mRNA Covid vaccines: https://papers.ssrn.com/sol...<br /> there was no significant protection from Covid death by the Pfizer and Moderna vaccines in their initial clinical trials, probably due to poor trial design, and these trials had a combined 37,000 subjects in both vax and placebo groups.

On 2022-07-08 01:11:17, user Sun Yeop Lee wrote:

"(ii) the sclerostin reducing alleles of the genetic variants were associated with increased BMD level"<br /> what is the rationale for applying this criterion for choosing genetic IVs? Is this because it is already known fact taht lowering sclerostin increases BMD?

just wondering what are the variants that lowers the sclerostin but decrease BMD

On 2022-07-20 17:40:27, user Elle Tigre wrote:

You suggest that, “In only a few cases, the presence of S1 or spike may be correlated with vaccination, however according to our previous findings, S1 is only detected within the first two weeks after the first dose and spike is rarely detected.”

An important takeaway from the study you referenced in your point is that none of the participants in that study had previous covid infection. So, it’s not that vaccination and boosters aren’t correlated with PASC or “Long covid” but, perhaps, previous infection, either before and/or after vaccination as well as an unvaccinated cohort, may be worthy of exploration? Especially considering your acknowledgement of non-PASC hospitalized participants having S1 and N, but no detectable full length spike protein, which is indicative of a typical “natural infection.” That should’ve flagged your suspicions. When exosomes can carry spike protein *at least* up to 4 months(though many have found it circulating much, much longer), don’t you think vaccination and boosting would prolong that circulation of spike protein? If spike protein, on its own, can cause pathogenesis, why don’t you suspect it can also cause, or at the very least, prolong PASC? At this point, your team should have more follow-up questions and reasonable suspicions from your study results than answers.

On 2022-08-10 17:46:53, user Prajwal Mani Pradhan wrote:

Thank you for all the comments and reviews. We have updated and <br /> published the study in a peer-reviewed journal. The updated study can be

accessed here at no extra cost:

https://pubs.lib.umn.edu/in...

On 2022-08-11 17:07:47, user Roman Kosoy wrote:

This article was accepted at Nature Genetics in July 2022 at: https://doi.org/10.1038/s41...

On 2021-05-04 21:26:25, user aleax wrote:

1 case out of 225 is 0.44%, definitely NOT 0.0041%.

On 2022-08-22 03:33:38, user BGThree wrote:

In Section 2.1 "Cell culture system to express SC2 proteins from synthetic mRNA-1273" the authors disclose incubation of mouse and human cells with 200uL vaccine, but do not disclose corresponding controls. Specifically, mouse and human cells should be incubated WITHOUT addition of vaccine. This control is needed to demonstrate the proteins extracted from lysed cells are transcribed from vaccine mRNA not innate mouse or human mRNA.

On 2020-04-02 13:15:38, user Sinai Immunol Review Project wrote:

COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome<br /> doi: https://doi.org/10.1101/202...

SUMMARY: This study is based on flow cytometry immunophenotyping of PBMCs from 28 patients diagnosed positive for SARS-Cov2 (COVID19). The authors identify a population of abnormally large (FSC-hi) monocytes, present in COVID19 patients, but absent in PBMCs of healthy volunteers (n=16) or patients with different infections (AIDS, malaria, TB). This FSC-hi monocytic population contains classical, intermediate and non-classical (monocytes (based on CD14 and CD16 expression) that produce inflammatory cytokines (IL-6, TNF and IL-10). The authors suggest an association of FSC-hi monocytes with poor outcome and correlate a high percentage of FSC-low monocytes, or higher ratio of FSC-low/hi monocytes, with faster hospital discharge.

LIMITATIONS: While identification of the monocytic population based on FSC is rather robust, the characterization of these cells remains weak. A comprehensive comparison of FSC-hi monocytes with FSC-low monocytes from patients and healthy controls would be of high value. It is unclear if percentages in blood are among CD45+ cells. Furthermore, it would have been important to include absolute numbers of different monocytic populations (in table 1 there are not enough samples and it is unclear what the authors show).<br /> The authors show expression of the ACE2 receptor on the surface of the monocytes, and highlight these cells as potential targets of SARS-Cov2. However, appropriate controls are needed. CD16 has high affinity to rabbit IgG and it is unclear whether the authors considered unspecific binding of rabbit anti-ACE2 to Fc receptors. Gene expression of ACE-2 on monocytes needs to be assessed. Furthermore, it would be important to confirm infection of monocytes by presence of viral proteins or viral particles by microscopy.<br /> Considering the predictive role of FSC-hi monocytes on the development of the disease and its severity, some data expected at this level are neither present nor addressed. Although the cohort is small, it does include 3 ICU patients. What about their ratio of FSC-low vs FSC-hi monocytes in comparison to other patients? Was this apparent early in the disease course? Does this population of FSC-hi monocytes differ between ICU patients and others in terms of frequency, phenotype or cytokine secretion? <br /> In general, figures need to revised to make the data clear. For example, in Fig. 5, according to the legend it seems that patients with FSC-high monocytes are discharged faster from the hospital. However according to description in the text, patients were grouped in high or low levels of FSC-low monocytes.

RELEVANCE : Despite the limitations of this study, the discovery of a FSC-high monocyte population in COVID-19 patients is of great interest. With similar implication, a the recent study by Zhou et al (https://www.biorxiv.org/con... "https://www.biorxiv.org/content/10.1101/2020.02.12.945576v1)") identified a connection between an inflammatory CD14+CD16+ monocyte population and pulmonary immunopathology leading to deleterious clinical manifestations and even acute mortality after SARS-CoV-2 infections. Although the presence of these monocytes in the lungs has yet to be demonstrated, such results support the importance of monocytes in the critical inflammation observed in some COVID19 patients.

Review as part of a project by students, postdoctoral fellows and faculty at the Immunology Institute of the Icahn school of medicine, Mount Sinai

On 2022-09-08 10:01:58, user Virgínia da Conceição wrote:

Published in the Health and Quality of Life Outcomes journal, DOI: 10.1186/s12955-022-01945-7

On 2022-09-27 14:27:59, user C. Downs wrote:

The published version can be accessed at Scientific Reports 10.1038/s41598-022-20214-7

On 2022-10-26 14:42:42, user Barbara Arch wrote:

Following peer review, the results and conclusions presented in this paper are currently under review. Further analysis is being undertaken and we will update the paper on completion of this additional work. <br /> Barbara Arch (lead author) & Prof MG Semple (Senior author and Study Sponsor CI)

On 2022-11-14 11:51:31, user Baral Nischit wrote:

The full manuscript is published and the PMCID is PMC9620387

On 2020-07-16 20:57:09, user Kate Webb wrote:

Really interesting- are the samples from MIS-C all before IVIG?

On 2020-07-18 17:50:20, user Matthew Almario wrote:

Who is the manufacturer of the UV light?

On 2023-05-15 01:46:49, user japhetk wrote:

This report is being used to promote the anti-vaccine movement.<br /> If the actual content is certain, it is indeed a concern and should be reported, but this study shows serious concerns.

First, this study does not take into account the number of tests. Given that the relationship between the number of vaccinations and the number of tests has been reported in many areas, this is the most serious flaw in this type of study and should be noted.<br /> Second, the results in Figure 2, which anti-vaccine activists focus on, is an inappropriate analysis that, as far as the methodology is concerned, only excludes uninfected persons from the unvaccinated population. We point out that this is one of the most serious problem of the study where the intent is clear and inappropriate.<br /> Furthermore, it is an attempt to statistically separate the effect of vaccination from the effect of previous infection, but this is not an appropriate method because many studies have reported that hybrid immunization does not show additive effects.<br /> The analysis in Figure 2 should have taken into account the history of infection and vaccination in the analysis comparing those with and without bivalent booster vaccination, but there should be no bivalent booster vaccination among the unvaccinated, which means that certain variables occurred only in one group. In this sense, this analysis is inappropriate.<br /> The raw data should be presented to show how many positives occurred among the unvaccinated, 3-dose uninfected, unvaccinated infected, 3-dose infected, etc. during the study period.<br /> Finally, this study cites a study that is convenient for cherry-picking and does not control for the number of tests, but the effect of vaccination history during this period is<br /> reported in Korea, Singapore, Japan, Luxembourg, and elsewhere, consistently contradicting the authors' results. The author's study is also inconsistent with the number of positive vaccine reports from Washington State and the CDC, which likewise do not take into account the number of tests.<br /> Bejko, Dritan, et al. "Effects of bivalent Omicron-containing vaccine boosters and prior infection against SARS-CoV-2 Omicron infections in Luxembourg, September-December 2022." Population Medicine 5.Supplement (2023).<br /> Tay, Matthew Zirui, et al. "Heterologous mRNA vaccine boosters induce a stronger and longer-lasting antibody response against Omicron XBB variant." The Lancet Regional Health–Western Pacific 33 (2023).<br /> Jang, Eun Jung, et al. "Estimated Effectiveness of Prior SARS-CoV-2 BA. 1 or BA. 2 Infection and Booster Vaccination Against Omicron BA. 5 Subvariant Infection." JAMA Network Open 6.3 (2023): e232578-e232578.<br /> https://covid.cdc.gov/covid...

All of the above make this study problematic and raise the concerns of improper statistical analysis for use in the anti-vaccine movement. We request that raw data by number of vaccinations and number of previous infections be presented. The study appears to have been published in a low impact factor journal, and if there is data on number of tests, that should also be presented.

On 2023-06-07 15:49:25, user Donald R. Forsdyke wrote:

These results are supported by a case history currently available at the Qeios preprint server<br /> Preprint

On 2023-06-20 09:28:49, user Matt Hodgkinson wrote:

The problem with this study, as others have noted on PubPeer, is that the authors are proposing a heuristic for identifying paper mill articles that fails under closer examination.

Prof Gigerenzer works on 'simple heuristics' and 'gut feelings' as a good approach to being smart: it seems that the authors thought this assessment was 'good enough' without thinking through the consequences of labelling so many authors as having committed misconduct with the wave of a hand.

It is possible that some journal editors will adopt such crude screening techniques and reject submissions that lack institutional email addresses and international authors, putting a further barrier in the way of authors from lower-income countries - and incentivising gift authorship. This would go against the spirit of the recent World Conferences on Research Integrity (WCRI) Cape Town Statement, including that "Barriers to ‘open science’ participation by researchers working in low-resource settings need to be identified and addressed by publishers, and other appropriate national and global stakeholders, such as science councils, funders, and similar institutions."

On 2023-07-11 19:31:39, user Sabrina Di Gregorio wrote:

This article has been published in https://doi.org/10.1099/mge...

On 2024-01-05 11:17:42, user William Cawthorn wrote:

The peer-reviewed manuscript based on this preprint has now been published here: https://doi.org/10.1016/j.c...

On 2020-06-14 16:39:26, user David Curtis wrote:

It is very important to realise that this is not a study of patients with COVID-19 - it is a study of patients who are hospitalised with COVID-19. Only a small fraction of patients with COVID-19 are hospitalised so this may be telling us something important about who ends up being hospitalised. You have this sentence: "Some researchers have postulated that ethnicity may be associated with decreased symptom recognition and poor health literacy resulting in delayed presentation for care-something that could contribute to the greater illness-severity we observed(30). " I would like to see much more attention devoted to this and related topics. What your data seem to show is that, of patients admitted with COVID-19, BAME patients are more likely to require ICU admission and are more likely to die. So an obvious question arises. Are BAME patients more unwell when they are admitted? Or, are white and BAME patients fairly similar at the time of admission but then the BAME patients are more likely to deteriorate? I do not see anything in your data which clearly answers this question. I feel that some aspects of the clinical assessment on admission would illuminate this but I don't know how easy it is to pull them out from the ECR.

To be blunt, let me state why I see this as an important issue. If BAME patients are more unwell when they are admitted then it points to problems with ensuring fair and equitable access to health interventions, here admission. You suggest that the fault might lie with the patients themselves - that their poor health literacy might result in delayed presentation. Maybe. But maybe this is victim-blaming. Maybe there are issues in the way healthcare is delivered and decisions about admission are made which make it harder for BAME people to get into hospital. I am not suggesting any deliberate racism on the part of health care professionals (though we should not completely discount this possibility). However we could consider that the way the gate-keeping around access to in-patient care is implemented results in a system which de facto disadvantages BAME patients. Obvious issues would be around language and ability to negotiate the 111 system. Perhaps there are issues with differential quality of services in primary care and the practices which BAME patients tend to be registered with. Perhaps there are communications issues with ambulance staff and 111 staff who are very influential regarding whether and when a patient gets to hospital to be assessed for admission.

This is a critical issue for our society and I hope you can somehow use the data you have to explore it. Have we created a system where it is harder for BAME patients to be admitted than white patients?

On 2020-04-28 15:32:51, user Sinai Immunol Review Project wrote:

Main findings<br /> In this manuscript, the authors describe direct complement system activation through the SARS-CoV-2-N-protein as a common denominator of coronavirus-induced lung injury.

The authors refer to previous evidence on SARS-CoV and MERS-CoV in which they showed that the nucleocapsid (N-) protein binds to a variant of MBL-associated serine protease-2 (MASP-2) that under physiologic conditions initiates the lectin pathway of the complement cascade. The authors hypothesized that SARS-CoV-2 activates the complement cascade in severely ill patients through viral N-protein-mediated dimerization and activating auto-cleavage of MASP-2 leading to respiratory failure in some patients.

Following confirmation of MASP-2 binding to the N protein of SARS-CoV, MERS-CoV and SARS-CoV2, the authors show that MASP-2/MBL binding is enhanced and subsequently demonstrate enhanced complement activation in vitro as measured by C4b deposition in a complement deposition assay and enhanced phagocyte activity. Translating these findings into an in vivo model, the authors pre-infected mice with an adenovirus expressing SARS CoV, MERS-CoV and control virus and challenged the animals with LPS to activate the lectin pathway. This effect was abolished when the N-protein was truncated or anti-MASP-2 antibodies or C1 esterase inhibitor (dissociates MASP from MBL) were used. In mice infected with SARS- or MERS-CoV, the authors found significantly higher C4b and C4 deposits in the lungs and showed tremendously worse survival. However, when MASP-2 knockout mice were challenged with the above-mentioned viruses (or C1 esterase inhibitor given), survival was substantially better as compared to virus-infected wildtype mice.

The authors next analyzed lung tissues from deceased COVID-19 patients and found strong IHC stainings of complement components. In the final step, the authors treated two critically ill COVID-19 patients with a monoclonal antibody that binds C5a (differs from the C5 convertase inhibitor eculizumab) as a part of a clinical trial. Both patients showed clinical improvement of their severe pneumoniae.

Limitations<br /> The question if and in how far coronaviruses are capable of activating the complement system has been controversial so far with conflicting data published.

However, the authors performed a thorough and convincing analysis with well-designed in vitro an in vivo experiments showing the ability of the nucleocapsid to enhance MBL initiated complement activation.

The authors performed key experiments using adenoviruses only containing SARS-CoV and MERS-CoV but not SARS-CoV-2. While the assumption that due to the high sequence homology in the N-protein-binding motif and the proven binding of the SARS-CoV-2 N-protein to MASP-2 strongly suggests that the N-protein in SARS-CoV-2 also plays a major role in complement activation in vivo remains to be proven.

MBL induced complement activation is likely to increase C3a and C3b formation as well as C5a and MAC complex deposition. The finding that anti C5a has some clinical benefit is of interest but does not directly support the MBL mechanism shown here (C5a production could occur via alternative or classical pathway activation)

Significance<br /> Anti-inflammatory treatment in patients with severe viral pneumonia is established as a clinical standard procedure. However, most pathophysiologic aspects of immune hyperreactivity in these patients remains unclear. The study reviewed here shows one mechanism by which coronaviruses activate the complement cascade causing or at least aggravating inflammation in the lung. Showing the successful treatment of two patients with a anti-C5a mAb (not available in the US) is promising and supportive of ongoing or planned trials of a cyclic peptide C3 inhibitor or a C5 convertase inhibiting monoclonal antibody (eculizumab) in severely ill COVID-19 patients.

Reviewed by C. Matthias Wilk, MD as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai. Edited by Professor P. S. Heeger, MD

References:<br /> doi: 10.1038/emi.2015.28. Epub 2015 May 6.<br /> doi: 10.1128/mBio.01753-18

On 2020-04-04 10:53:48, user Statistics wrote:

almost 80% at the cross test(!)... so what about Iris diagnosis? Tuberculosis was over 80 % back in the 50s... so if anyone has time to evalute (complete time table please) I will appreciate; also check the completeness of the waldeyer throat ring of the infected; just for the interest...have thanks and praises

On 2020-04-04 19:45:40, user Ibraheem Alghamdi wrote:

That is the thing with ecological studies, they are good at generating hypotheses and interesting, but, they prove nothing.

On 2020-04-04 22:05:26, user PhilipandHeidi Kapitaniuk wrote:

Here in France the BCG has been widely used, and we still are losing many people to the Coronavirus. They need to be looking at more than just a few countries. This does not sound serious to me.

On 2020-04-07 16:26:34, user Richard wrote:

they stopped the BCG vaccination in australia in 1982, interesting that the death rates in australia amongst the older people are lower than seen in other countries,

On 2020-03-30 15:52:29, user Rosemary TATE wrote:

Hi, I have just performed a review of this preprint. I hope it is useful. I'm a medical statistician. I'd certainly like to see the next version, and it would be good if you could take my comments on board. I'd be happy to help with the stats if you need it.

On 2020-04-01 18:41:26, user Ronald McCoy wrote:

This totally glosses over China. Huge case numbers with universal BCG vaccination. This is a classic example fo confirmation bias. This article has more holes than a Swiss cheese factory.

On 2020-04-02 17:08:35, user Yaira Ca Ce wrote:

Interesting correlation BUT... Is it strong enough the correlation of data from countries in different stages? Being from Mexico makes me think of the lack of detection in my country. The tests haven't been applied massively, and there are MANY cases of atypical pneumonia and flu. Interesting isn't it? It might be that a low morbility and mortality is due to under developed countries in their first stages or there's not a massive testing. Still interesting to consider it. At the end it will be more realistic to make a comparison.

On 2020-04-05 19:18:00, user Sinai Immunol Review Project wrote:

Main Findings: <br /> The study compares IgM and IgG antibody testing to RT-PCR detection of SARS-CoV-2 infection. 133 patients diagnosed with SARS-CoV-2 in Renmin Hospital (Wuhan University, China) were analyzed. The positive ratio was 78.95% (105/133) in IgM antibody test (SARS-CoV-2 antibody detection kit from YHLO Biotech) and 68.42% (91/133) in RT-PCR (SARS-CoV-2 ORF1ab/N qPCR detection kit). There were no differences in the sensitivity of SARS-CO-V2 diagnosis in patients grouped according to disease severity. For example, IgG responses were detected in 93.18% of moderate cases, 100% of severe cases and 97.3% of critical cases. In sum, positive ratios were higher in antibody testing compared to RT-PCR detection, demonstrating a higher detection sensitivity of IgM-IgG testing for patients hospitalized with COVID-19 symptoms.<br /> Limitations of the study:<br /> This analysis only included one-time point of 133 hospitalized patients, and the time from symptom onset was not described. There was no discussion about specificity of the tests and no healthy controls were included. It would be important to perform similar studies with more patients, including younger age groups and patients with mild symptoms as well as asymptomatic individuals. It is critical to determine how early after infection/symptom onset antibodies can be detected and the duration of this immune response.<br /> Relevance:<br /> The IgM-IgG combined testing is important to improve clinical sensitivity and diagnose COVID-19 patients. The combined antibody test shows higher sensitivity than individual IgM and IgG tests or nucleic acid-based methods, at least in patients hospitalized with symptoms. <br /> Review by Erica Dalla as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn school of medicine, Mount Sinai.

On 2020-04-05 22:01:17, user Kirsten McEwen wrote:

Can the authors provide power analysis?

On 2020-04-06 11:27:18, user Eleanor Johns wrote:

"Conclusion: The SARS-CoV-2 prevention needs to focus on the screening of asymptomatic patients in the community with a history of contact with the imported population, especially for children and the elderly population." 28% of infected COVID19 individuals are asymptomatic, as PCR and Antibody testing covered a wide population in a Chinese province. We must test EVERYONE.

On 2020-04-06 14:39:20, user Jason Kidde wrote:

It would be interesting to see how blood type applies along age groups with regard to disease severity and death. If the finding is preserved across age groups, this would add muster. Additionally, I'm curious about looking into death rates and severity across geographic regions. For instance how much does blood type explain the death rates in Eastern Europe being that the type A allele is more common in this region, while the type A allele virtually does not exist in South America. Will this result in lower death rates in South America? So far Brazil has a fairly average death rate (4%) compared to other nations whereas Chile's is quite good at 0.7%. I realize that many other factors effect this, principally the testing vs true total disease as well as healthcare infrastructure.

On 2020-03-25 12:29:20, user jenniepoole wrote:

Hi were any of the patients with <br /> type A also checked for RH negative or were they all A + ?? This is important to me.

On 2020-03-25 15:31:18, user Sinai Immunol Review Project wrote:

These authors compared the ABO blood group of 2,173 patients with RT-PCR-confirmed COVID-19 from hospitals in Wuhan and Shenzhen with the ABO blood group distribution in unaffected people in the same cities from previous studies (2015 and 2010 for Wuhan and Shenzhen, respectively). They found that people with blood group A are statistically over-represented in the number of those infected and who succumb to death while those with blood group O are statistically underrepresented with no influence of age or sex.

This study compares patients with COVID-19 to the general population but relies on data published 5 and 10 years ago for the control. The mechanisms that the authors propose may underlie the differences they observed require further study.

Risk stratification based on blood group may be beneficial for patients and also healthcare workers in infection control. Additionally, investigating the mechanism behind these findings could lead to better developing prophylactic and therapeutic targets for COVID-19.

On 2020-03-27 00:50:17, user Simon Brazendale wrote:

I read this paper quickly and feel that people need to keep an open mind either way, the question is 'can this finding be reproduced?'. Certainly meta analysis seems to have been achieved, but the I squared values are greater than 25% for blood groups A and AB, which suggests some heterogenity. Lets see if out this global tragedy other studies can reproduce this as well as the original finding needing further scrutiny. It may be part of a key to better understanding or just a red herring

On 2020-04-03 03:05:56, user Philomena Okeke wrote:

I like more studies and research to be done on this.If group A+ are vulnerable then they should be protected from this Coronavirus.The B and O should really help especially the 0 group. I am sure that more researchers need to provide more evidence on this critical issues. <br /> Thanks

On 2020-04-06 18:50:06, user Theodore Koukouvitis wrote:

Insightful and readily quantifiable. The author is confident enough to make specific, short-term predictions and warn against the danger of a full removal of social distancing measures.

This paper should be peer reviewed and evaluated ASAP.

On 2020-04-06 18:54:14, user Sinai Immunol Review Project wrote:

This study examined antibody responses in the blood of COVID-19 patients during the early SARS CoV2 outbreak in China. Total 535 plasma samples were collected from 173 patients (51.4% female) and were tested for seroconversion rate using ELISA. Authors also compared the sensitivity of RNA and antibody tests over the course of the disease . The key findings are:

• Among 173 patients, the seroconversion rates for total antibody (Ab), IgM and IgG were 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively.

• The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. Overall, the seroconversion of Ab was significantly quicker than that of IgM (p = 0.012) and IgG (p < 0.001). Comparisons of seroconversion rates between critical and non-critical patients did not reveal any significant differences.

• RNA tests had higher sensitivity in early phase and within 7 days of disease onset than antibody assays (66.7% Vs 38.3% respectively).

• The sensitivity of the Ab assays was higher 8 days after disease onset, reached 90% at day 13 and 100% at later time points (15-39 days). In contrast, RNA was only detectable in 45.5% of samples at days 15-39.

• In patients with undetectable RNA in nasal samples collected during day 1-3, day 4-7, day 8-14 and day 15-39 since disease onset, 28.6% (2/7), 53.6% (15/28), 98.2% (56/57) and 100% (30/30) had detectable total Ab titers respectively Combining RNA and antibody tests significantly raised the sensitivity for detecting COVID-19 patients in different stages of the disease (p < 0.001).

• There was a strong positive correlation between clinical severity and antibody titer 2-weeks after illness onset.

• Dynamic profiling of viral RNA and antibodies in representative COVID-19 patients (n=9) since onset of disease revealed that antibodies may not be sufficient to clear the virus. It should be noted that increases in of antibody titers were not always accompanied by RNA clearance.

Limitations: Because different types of ELISA assays were used for determining antibody concentrations at different time points after disease onset, sequential seroconversion of total Ab, IgM and IgG may not represent actual temporal differences but rather differences in the affinities of the assays used. Also, due to the lack of blood samples collected from patients in the later stage of illness, how long the antibodies could last remain unknown. For investigative dynamics of antibodies, more samples were required.

Relevance: Total and IgG antibody titers could be used to understand the epidemiology of SARS CoV-2 infection and to assist in determining the level of humoral immune response in patients.

The findings provide strong clinical evidence for routine serological and RNA testing in the diagnosis and clinical management of COVID-19 patients. The understanding of antibody responses and their half-life during and after SARS CoV2 infection is important and warrants further investigation

On 2020-04-07 23:26:41, user Sam Raredon wrote:

Here is a video briefly showing and describing the technique:

PReVentS Circuit Demonstration - COVID-19 / Yale / Niklason Lab<br /> https://www.youtube.com/wat...

On 2020-04-07 23:34:20, user Karl Riley wrote:

It's worth looking at the benefits of a strategic infection variant, whereby those known to be at least risk of death are exposed to the virus in a controlled environment and then 'released' back into the general population thereby facilitating herd immunity. You could even have those, then known to be immune, as a form of shield in areas looking imminently vulnerable (hospital admission figures could be part of the data used for this) to the spread of the infection.