On 2022-10-13 01:36:58, user Renier Mendoza wrote:

Now published in PeerJ <br /> https://doi.org/10.7717/pee...

On 2021-08-11 01:45:23, user Sli wrote:

Would be useful if you add a table listing the time from full vaccination for all those green dots beyond 10 days.

On 2020-11-23 20:10:20, user TheMeerkat wrote:

To me the graphs in the pdf look like random distribution. I have no clue how anyone could decide that there is any correlation between values on two axes unless they decided it would be there before starting this research.

On 2020-11-30 01:00:57, user lbaustin wrote:

Does your hospital not routinely check vitamin D status - 25(OH)D levels? Recent studies have shown that if vitamin D is given early, it can decrease Covid-19 severity, but it is far less effective in severely ill patients.

On 2023-01-14 13:18:53, user Basheer Marzoog wrote:

the paper is published https://www.eurekaselect.co...

On 2021-08-12 13:33:46, user brikz wrote:

Yep, the PHD factor stood out to me as well. Love to hear why that is.

On 2021-08-13 05:55:13, user Joseph Akins wrote:

The PhD finding is not surprising. Given how most PhDs live their lives the difference in getting the vaccine vs not getting it may be viewed as negligible. That pro vaccine "arguments" broadly fall into one of three logical fallacies there is reasonable skepticism as to the motivation behind them. The three basic fallacies used are: appeals to authority, appeals to sentiment and ad hominem attacks.

Additionally, those with PhDs are hopefully trained to not be fooled by logical fallacies and those that have no university "education" have not been brain washed to mindlessly find them compelling (at least that's what 10 years enlisted in the military showed me).

Those with PhDs in the sciences are more likely to understand that science is a process and cannot "say" anything and is only "followed" by fools. This is similar to David Hume's idea that "you cannot derive an ought from an is". How the world operates tells us nothing about what we ought to do in any situation including whether any particular individual "ought" to get vaccinated, or wear a mask.

Those with PhDs in non STEM related fields are in my opinion, as one with a PhD in the physical sciences, much more likely to see science as a social instrument and probably support vaccine promotion and even coercion. Unfortunately, too many people, in general, ignorantly see science as an instrument with which they can bludgeon their political adversaries. This is willful ignorance that results in people being treated as means towards an end and not as thinking people with their own ends in mind.

I not only have a PhD, but I left Academia and have worked as a Registered Nurse for over 15 years. As to whether I personally believe in vaccines is of no importance because the disagreement is actually not over vaccines, or masks, but over the millenia old tension between individual autonomy and the collective "good". I fall squarely on the side of individual autonomy and against arguing by logical fallacies regardless of any view on whether I ought to get a vaccine. That I, on occasion, actually take care of COVID positive ICU patients is not a factor most people need to consider.

On 2023-01-30 12:28:48, user Aniko Lovik wrote:

This preprint has been now published in Stress and Health after peer-review: https://doi.org/10.1002/smi...

On 2020-07-18 05:45:16, user Peter Lange wrote:

Those last 2 #covid symptom clusters associate strongly with frailty... seems frailty and covid are associated with delirium and poor outcome. Not sure structuring as "symptom clusters" helps

On 2021-12-07 11:30:00, user kdrl nakle wrote:

This paper is not worth much as the authors failed to collect any real world data. It is not easy but that is something that needs to be done instead of replacing it with hypothesizing this or that.

On 2020-06-02 19:28:30, user lfstevens wrote:

Would like to see the definition of "high" and "low". A concentration? Or just "early" or "late".

On 2023-07-21 14:12:39, user Gaël Nicolas wrote:

I think that this variant is definitely a strong contributor to AD. However, the pedigrees also show that the patients with DNA available and carrying the variant, also carry one APOE4 allele. Actually, APOE4 segregates as good as SORL1 in these pedigrees! All affected individuals with DNA available are SORL1+/APOE4+. One unaffected individual is SORL1+/APOE4- (family 1) and one unaffected individual is SORL1-/APOE4+ (family 2). To be clear, I have absolutely no doubt of a major role of the SORL1 variant here, but I feel that this is very much consistent with a more complex inheritance and not purely autosomal dominant, as shown in our penetrance paper (Schramm et al., Genome Medicine 2022, PMID 35761418)

Interestingly, we have the same variant in three independant families from France (one of them is mentioned in this preprint). Although there is an obvious aggregation of AD cases in the families, there is a huge diversity of ages of onset and younger cases have a positive family history in both branches, suggesting the contribution of additional factors. Some of them are APOE4+ but not the 2 youngest probands. This may suggest the contribution of undetected contributing variants along with SORL1.

Overall, our penetrance paper (Schramm et al., 2022) and many pedigrees suggest a contribution of additional factors with SORL1 variants and that SORL1 alone may not be sufficient / fully penetrant. We have clear evidence for APOE4, as this is a common allele, but we know that there are many other other AD-associated variants, especially rare variants, among known variants (as families with SORL1+ABCA7 as we previously reported in Campion et al., Acta Neuropath 2019, PMID 30911827) and in other papers and, obviously, not yet known variants.

I thus recommend to use such results with great caution for genetic counseling, as we still don't exactly know how variants in other genes may drastically change an age of onset from 50 to 75-80 for example, or to absence of AD (as also shown for some truncating variants, as in Campion et al., 2019 where a mother transmitted a truncating a truncating variant and was unaffected with AD at age 95 years).

On 2021-12-16 12:09:06, user Ichizo Nishino wrote:

Now the paper has been published online in Neurology.<br /> https://pubmed.ncbi.nlm.nih.gov/34873015/

On 2020-06-03 17:13:16, user Euclides Castilho wrote:

cases according the results of the survey is not the same that the official statistcs say. These are cases according the surveillance definition . Official statistics do not take in account "infected" people

On 2020-06-05 18:57:05, user Paul Gordon wrote:

Hi, nice work. One minor clerical issue you may want to address is that in Supplemental Table 2, the GISAID IDs for UC1-11 are incorrect (all have the same ID as UC12).

On 2020-06-05 20:58:26, user eduardo wrote:

Comment from author: new version (uploaded 04 June 2020) updated parameters based on new data; the main difference with the first version is that the "CID" critical delay is now shorter, but nothing changed qualitatively.

On 2020-04-10 09:17:04, user Rosemary TATE wrote:

Authors could you please provide me with the CSV data file that I requested in an email to the corresponding author on Monday. Or better still could you please upload it?<br /> Thanks

On 2020-04-10 22:18:29, user stephenkirby wrote:

We're seeing a lot of curves on Coronavirus right now, but I'm just wondering, are there similar stats of influenza this year that would be helpful for people's perspectives?

On 2021-01-22 03:19:14, user Roberto wrote:

Ok but, whats is this? More than 200 scientifics and academic articles saying HDC is effective for COVID-19? https://c19study.com

On 2020-08-26 08:35:30, user joejoe3 wrote:

Are you saying death data is given the death date as the time of data entry? Doesn't that seem completely irresponsible practice? Who would ever do that? Isn't the actual death date/time very prominent on the chart? Always???

On 2019-10-17 08:06:25, user Øystein Haaland wrote:

Paper published in PLOS ONE.

On 2020-01-07 12:53:20, user Guyguy wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI ON 05 JANUARY 2020

Monday, January 06, 2020

• Since the start of the epidemic, the cumulative number of cases has been 3,390, including 3,272 confirmed and 118 probable. In total, there were 2,233 deaths (2,115 confirmed and 118 probable) and 1,114 people healed;<br /> • 373 suspected cases under investigation;<br /> • 2 new confirmed cases in Ituri in Mambasa;<br /> • No new deaths among the confirmed cases, including:<br /> o No community deaths have been recorded;<br /> o No death among the confirmed cases;<br /> • No healed person has left the CTE;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 164 (approximately 5% of all confirmed / probable cases), including 41 deaths;<br /> • Mambasa again reported a confirmed case after 66 days of silence.

NEWS<br /> Organization of an evaluation session of awareness-raising activities in the Malepe health area in Beni<br /> • The sub-coordination of the response to the Ebola virus disease epidemic organized this Monday 06 December 2020 an evaluation session of awareness-raising activities in the Malepe health area in Beni;<br /> • According to the Coordinator of this Sub-coordination, Dr. Pierre-Céleste Adikey, this evaluation aims to intensify surveillance around visitors and raise alerts. These strategies, he said, will strengthen measures to protect the City against any possible reinfection of the City;<br /> • On this occasion, it was announced the resumption of free healthcare within the Malepe health center with the support of the NGO ALIMA which, from now on, provides drugs for the free care of the sick;<br /> • In addition, the Ebola Treatment Center (CTE) in Mangina unloaded the first eight Ebola winners in 2020 on Monday. These survivors, who were reintegrated into their respective communities, notably in Aloya / Canteen, testified to good care within this CTE.

VACCINATION<br /> • 4,802 people were vaccinated, until January 2, 2020, with the 2nd vaccine Ad26.ZEBOV / MVA-BN-Filo (Johnson & Johnson) in the two health areas from Karisimbi to Goma;<br /> • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 261,596 people have been vaccinated;<br /> • Approved on October 22, 2019 by the Ethics Committee of the School of Public Health at the University of Kinshasa and on October 23, 2019 by the National Ethics Committee, the second vaccine, called Ad26.ZEBOV / MVA-BN -Filo, is produced by Janssen Pharmaceuticals for Johnson & Johnson;<br /> • This new vaccine complements the first, rVSV-ZEBOV, a vaccine used until then (since August 08, 2018) in this epidemic manufactured by the pharmaceutical group Merck, after approval by the Ethics Committee on May 20, 2018. It was recently pre-qualified for certification.

ENTRY POINT SURVEILLANCE<br /> • Since the start of the epidemic, the total number of travelers checked (temperature measurement ) at health checkpoints has been 135,503,900 ;<br /> • To date, a total of 109 entry points (PoE) and health control points (PoC) have been established in the provinces of North Kivu and Ituri in order to protect the country's major cities and avoid the spread of the epidemic in neighboring countries.

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

1. Respect basic hygiene measures, in particular regular hand washing with water and soap or ash;
2. If an acquaintance from an epidemic area comes to visit you and that he is sick, do not touch him and call the toll-free number for civil protection in North Kivu;
3. If you are identified as a contact with an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If someone dies due to Ebola, follow the guidelines for dignified and secure burials. It is simply a mode of burial that respects funeral customs and traditions while protecting the family and the community from Ebola contamination.
5. For all health professionals, observe hygiene measures in health centers and report any sick person showing 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 12:11:25, user GuyguyKabundi Tshima wrote:

EPIDEMIOLOGICAL SITUATION

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT OCTOBER 06, 2019<br /> Monday, October 07, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,205, of which 3,091 are confirmed and 114 are probable. In total, there were 2,142 deaths (2028 confirmed and 114 probable) and 1006 people healed.<br /> 363 suspected cases under investigation;<br /> 1 new confirmed case at CTE in North Kivu at Oicha;<br /> No new confirmed deaths<br /> 2 people healed from Butembo CTE;<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

7 people healed from Ebola Virus Disease released Monday at Komanda CTE<br /> - A total of 7 people cured of Ebola Virus Disease were released on Monday October 7th at the Ebola Treatment Center (ETC) in Komanda. ;<br /> - This is 4 people from Mambasa and 3 cases from Komanda Health Zone to whom discharge certificates were given by the director of this Ebola Treatment Center<br /> - This certificate of discharge bears as inscription: "On the date of issue of this document the bearer of this certificate does not present any risk of contaminating other people, because his test was negative for the Ebola virus disease. He / she is thus DECLARE GUERI (E) . His current state of health is not a danger to the community. That is why he / she can return to his household and his professional environment to continue the daily activities. The family, the community and the authorities are asked to welcome him to promote his social integration ".

VACCINATION

• Continuation of vaccination around the confirmed case of 04 October 2019 in the Tenambo Health Area in Oicha, North Kivu;
• Continuation of the vaccination of newly recruited front-line staff at the General Reference Hospitals of Katwa and Kyondo in North Kivu;
• Since vaccination began on 8 August 2018, 234,693 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 increase) at the sanitary control points is 103,167,809 ;
• 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 2019-10-17 18:36:39, user GuyguyKabundi Tshima wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS OF OCTOBER 15, 2019

Wednesday, October 16, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,227, of which 3,113 are confirmed and 114 are probable. In total, there were 2,154 deaths (2040 confirmed and 114 probable) and 1038 people healed.<br /> 530 suspected cases under investigation;<br /> 3 new confirmed cases, including:<br /> No cases in North Kivu;<br /> 3 in Ituri in Mandima;<br /> 1 new confirmed death, of which:<br /> 1 community death in Ituri in Mandima;<br /> No confirmed deaths;<br /> 2 people healed from the 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

The state of play of the response at the center of an interview in Goma between the Technical Secretary of the CMRE and the United Nations Emergency Coordinator for Ebola<br /> - The Technical Secretary of the Multisectoral Committee on Epidemic Response to Ebola Virus Disease (ST / CMRE), Prof. Jean Jacques Muyembe Tamfum, granted a hearing on Wednesday, October 16, 2019 in Goma to the United Nations Emergency Coordinator for Ebola;<br /> - During their meeting, the two personalities discussed the state of play of the response to the 10th Ebola Virus Disease outbreak and the security situation in the areas affected by this epidemic;<br /> - It should be noted that the 10th Ebola epidemic has been taking place in the Democratic Republic of the Congo in areas of armed conflict, particularly in the provinces of North Kivu and Ituri, for more than a year;<br /> - Some time before this meeting, the technical secretary of the Multisectoral Committee for the Response to the Ebola Virus Disease Epidemic (ST / CMRE), Prof. Muyembe Tamfum, who is currently staying in Goma, North Kivu to inquire about the evolution of the response, chaired the morning meeting of the general coordination of the Ebola response to the epidemic.

Pygmies at Mahombo camp in Mambasa territory in Ituri pledge to fight Ebola Virus Disease

• The pygmies residing in Mahombo camp located more than 30 minutes walk from the main road from the village Nyangwe in the territory of Mambasa in ITURI, pledged Tuesday, October 15, 2019 to fight against Ebola by raising alerts with teams of the response;<br /> This commitment is the result of awareness raising by the Community Risk and Commitment (CREC) teams for 79 pygmies about the generalities of the Ebola virus disease, its methods of prevention and contamination;<br /> Pygmies have, for this purpose, asked for hand washing kits to break the chain of transmission of the Ebola virus in their respective communities.

VACCINATION

• Since vaccination began on 8 August 2018, 238,700 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

• The Governor of North Kivu, Carly Nzanzu Kasivita accompanied by a strong delegation, visited Maboya Control Points (PoCs) in Kalunguta and Kangote in Butembo in North Kivu Province;
• The providers of the Mususa Point of Control (PoC) in Butembo, North Kivu, in collaboration with the Ndondo Primary School and the Kyambogho School Complex, participated in a mass sensitization session (travelers and riverside population) under the theme " All Eliminate Ebola Virus Disease "on International Handwashing Day;
• Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 106.625.956 ;
• 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 2019-11-17 04:20:48, user GuyguyKabundi Tshima wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT NOVEMBER 15, 2019<br /> Saturday, November 16, 2019<br /> • Since the beginning of the epidemic, the cumulative number of cases is 3,292, of which 3,174 are confirmed and 118 are probable. In total, there were 2,195 deaths (2077 confirmed and 118 probable) and 1070 people healed.<br /> • 517 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 CTEs;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 163 (5% of all confirmed / probable cases), including 41 deaths.

NEWS

Goma opens leadership capacity building workshop for Ebola epidemic response to Ebola Virus Disease.

• The coordinator of the epidemic response to Ebola Virus Disease in North and South Kivu Province and Ituri, Prof. Steve Ahuka Mundeke, opened this Saturday, November 16, 2019 in Goma North Kivu a workshop on building the capacity of actors involved in the response against Ebola;<br /> • For four days, participants, coordinating and sub-coordinating officers from the response, the Ministry of Health, the World Health Organization (WHO), national security, CDC and DFID will be equipped with management skills epidemics before, during and after the tenth epidemic of Ebola Virus Disease, especially in the event of any outbreak;<br /> • According to Prof. Ahuka, this workshop will not only benefit this epidemic, but will help, through acquired skills, to cope with other epidemics or other crises in a collective and individual way. " Each participant will be able to use these skills in his daily life ," he concluded;<br /> • This training for the response officers, from 16 to 20 November 2019, is organized by the Ministry of Health in collaboration with WHO with funding from UKaid from the British people.

VACCINATION

• 93 people were vaccinated with the 2nd Ad26.ZEBOV / MVA-BN-Filo vaccine (Johnson & Johnson) in the two Health Zones of Karisimbi in Goma;<br /> • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 252,835 people have been vaccinated;<br /> • Approved October 22, 2019 by the Ethics Committee of the School of Public Health of the University of Kinshasa and October 23, 2019 by the National Ethics Committee, the second vaccine, called Ad26.ZEBOV / MVA-BN -Filo, is produced by Janssen Pharmaceuticals for Johnson & Johnson;<br /> • This new vaccine complements the first, the rVSV-ZEBOV, vaccine used until then (since August 08, 2018) in this outbreak, manufactured by the pharmaceutical group Merck, after approval of the Ethics Committee on May 20, 2018. It has recently been approved.

MONITORING AT ENTRY POINTS

• Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 117,333,420 ;<br /> • To date, a total of 112 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 2019-11-30 16:39:58, user Guyguy wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT NOVEMBER 26, 2019<br /> Wednesday, November 27, 2019<br /> • Since the beginning of the epidemic, the cumulative number of cases is 3,304, of which 3,186 are confirmed and 118 are probable. In total, there were 2,199 deaths (2081 confirmed and 118 probable) and 1077 people cured.<br /> • 366 suspected cases under investigation;<br /> • No new confirmed cases;<br /> • No new deaths among confirmed cases;<br /> • No cured person has emerged from CTEs;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 163 (5% of all confirmed / probable cases), including 41 deaths.

NEWS

Closure of training of Ebola Rapid Response Teams in Goma

• The Ebola response coordinator for the Ebola response to operations, Dr. Luigino Mikulu, closed on Wednesday 27 November 2019 the training of Rapid Response Teams (RRTs), composed of units of the Armed Forces. (FARDC) and the Congolese National Police (PNC), on the Ebola virus disease that took place in Goma, capital of North Kivu Province from 22 to 26 November 2019;<br /> • For Dr. Luigino, this team is the first in the Rapid Response Teams to be composed of elements from other sectors, such as those of the Ministries of Defense and Security and the Ministry of the Interior;<br /> • This training aligns with the vision of the Technical Secretariat of the Multisectoral Ebola Virus Disease Response Committee (ST / CMRE), through the overall coordination of the response, to expand its mixed and multidisciplinary teams available and able to intervene 24 hours a day, 7 days a week and everywhere, where they will be deployed, not only for the response to this epidemic to Ebola Virus Disease, but also for other epidemics;<br /> • This training was a pride for WHO to accompany the Ministry of Health in order to capitalize the capacity building of FARDC and PNC units in public health;<br /> • The participants, in turn, reassured the overall coordination of the response, the Ministry of Health and all those who contributed to the delivery of this training, particularly to WHO and all facilitators, to be faithful disciples in the field by putting into practice all the notions learned during these sessions;<br /> • At the end of this training, the thirty participants, including the facilitators, received a participation certificate.

VACCINATION

• Despite the tense situation of the city of Beni, a vaccination ring was opened around the confirmed case of 24 October 2019 in the Kanzulinzuli Health Area of the General Reference Hospital;<br /> • 724 people were vaccinated, until Tuesday, November 26, 2019, with the 2nd Ad26.ZEBOV / MVA-BN-Filo vaccine (Johnson & Johnson) in the two health zones of Karisimbi in Goma;<br /> • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 255,247 people have been vaccinated;<br /> • Approved October 22, 2019 by the Ethics Committee of the School of Public Health of the University of Kinshasa and October 23, 2019 by the National Ethics Committee, the second vaccine, called Ad26.ZEBOV / MVA-BN -Filo, is produced by Janssen Pharmaceuticals for Johnson & Johnson;<br /> • This new vaccine is in addition to the first, the rVSV-ZEBOV, vaccine used until then (since August 08, 2018) in this epidemic manufactured by the pharmaceutical group Merck, after approval of the Ethics Committee on May 20, 2018. has recently been pre-qualified for registration.

MONITORING AT ENTRY POINTS

• Sanitary control activities are disrupted in the towns of Beni and Butembo in North Kivu province following demonstrations by the population which decries killings of civilians;<br /> • Since the beginning of the epidemic, the total number of travelers checked (temperature measurement ) at the sanitary control points is 121,159,810 ;<br /> • To date, a total of 109 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 2020-01-25 07:04:43, user Roc Duan wrote:

Considering only air travel may have significantly distorted the model. As a result, it may incorrectly predict a faster spread.

On 2020-01-31 12:47:48, user Jonathan Li wrote:

Hi, how can I download this article? Very interested to read details because my prediction is it reaches peak point around 6th March then ends on early June. Thanks.

On 2020-02-02 13:28:10, user lily absence wrote:

Dear authors:<br /> I want to know the details of the model, where can I find Methods Supplement?

On 2020-02-13 11:26:17, user ClosedCloak wrote:

I couldn't find any information about the data of bed numbers in 99.com.cn. The authors should clarify it.

On 2020-03-13 02:25:01, user Thomas J Janstrom wrote:

In light of the index patient now being traced back to a 55yo male in Wuhan who became symptomatic on the 17/11/2019 how will this alter the predicted cases as per your paper?

On 2020-05-13 18:37:05, user Matthew Spinelli wrote:

Would recommend you present odds ratios from your conditional logistic regression instead of an unmatched t-test in table 2. Important work!

On 2021-07-28 14:18:10, user H. wrote:

5,372 were excluded from study due to infection how many had any vaccine? 795 not considered vaccinated how many had vaccine injection? These are important questions.

On 2021-07-29 23:48:53, user Nicholas Morrish wrote:

What if the IgG you were reading was from something else, like SV40? Anecdotal evidence of pregnant women tested in the same regions showed that roughly ~10% of the populace had a SV40 infection.

On 2020-10-21 23:20:22, user Melimelo wrote:

Very useful study. Any chance you could do this study with warm salt water as one of the gargling solutions? maybe try different salt concentrations?

On 2020-04-21 20:54:48, user Dr. Héctor Musacchio wrote:

I am confused about the interpretation of this study. Asymptomatic people who are tested, most likely are false positives. I would like to know the opinion of the authors

On 2020-04-17 23:52:12, user Daniel H Vlad, PhD wrote:

Dear Author, <br /> I appreciate your efforts to shed light on this very important topic but I believe the article has a major bias, which is indeed mentioned in the article.<br /> "Other biases, such as ... bias favoring those with prior COVID-like illnesses seeking antibody confirmation are also possible. The overall effect of such biases is hard to ascertain. "

I think this is a very serious bias and let me explain why. It's very likely that your Facebook ads attracted a fair number of participants that were concerned they may have been infected with Covid-19. People who had experienced Covid-like symptoms in the recent past were more likely to pay attention to your Facebook ad and were also more likely to enroll in your study. Therefore your sample is not random.<br /> Let's make some reasonable assumptions. Let's assume that 10% of your sample, or 333 participants had Covid-19 like symptoms in the past and were seeking antibody confirmation. I believe this percentage is very reasonable. <br /> According to California statistics, approximately 25% of people tested for Covid-19 test positive. It could be very reasonable to assume that 15% of these 333 participants seeking antibody confirmation had been indeed infected. So that will equal to 50 positive participants, or the entire number of antibody test positive participants in your sample.<br /> The example above proves that this bias is a valid concern. Your entire list of 50 antibody positive participants could have been participants seeking antibody confirmation.

There are several ways to remove the bias:<br /> a. You mention in the article that you asked survey participants if they had prior clinical symptoms. You should try to exclude all participants that had symptoms (fever, chest pressure) similar to Covid-19 this year. This will indeed exclude all people that were ill, not only those who replied to the add to seek antibody confirmation. However, it will give you insight into the percentage of silent Covid-19 carriers, which is a question as important as the question you are trying to answer, and in a way equivalent. And the results will be unbiased. <br /> b. Attempt to adjust for this bias. Calculate the percentage of participants in your sample who experienced Covid-19 symptoms and compare this with reasonable epidemiological data. Calculate a weight and apply it to your sample in addition to your zip-sex-race weights.

Regards, Daniel H. Vlad, PhD.

On 2020-04-18 17:13:58, user Animesh Ray wrote:

I do not believe these conclusions. A crucial control for the estimate of false positive detection by their method is grossly inadequate. This manuscript should not have seen the light of the day in this form, let alone be published even in a pre-print format because of the sensitivity of the topic.

Here is the reason: The common cold coronaviruses that could potentially cross-react to existing pre-COVID19 IgM/IgG are quite prevalent in the population. To address this, the authors tested 30 pre-COVID19 sera.

Given an unadjusted detection rate of 2.8% seropositives in post-COVID-19 samples, if all were false positives, they needed to test, for 99% confidence, a MINIMUM of log(0.01)/log(0.972) = 162 pre-COVID19 sera of similar demographics (age/sex/location).

Instead, they tested only 30!

[They do cite the kit validation data by the supplier/vendor as having tested 371 negative samples--this is as spurious an argument as stating that a q.RT-PCR kit produced x frequency of true negatives by the supplier and therefore we don't need to do the appropriate control in our experiment!! This statement has no place in a scientific publication other than trying to obfuscate the real weight of the lack of sufficient control to determine the false positive rates.]

On this basis I cannot attach any value to this report.

These false conclusions, given the current pre-print version, are dangerous because they could be naively interpreted to imply a lesser morbidity of COVID19 than the current numbers otherwise suggest.

I fear that this pre-print will now be used by the public media and sections of political interest groups to advocate for lesser stringency in COVID-19 pandemic control than desirable, and might lead to unfortunate loss of lives.

On 2020-04-21 15:33:02, user ?????Ozymandias????? wrote:

I'm just an undergrad with no expertise, but based on Bayesian logic, when the sensitivity of a test isn't perfect, and given the low prevalence of a trait in a population, won't the test tend to elicit enough false-positives to cloud the results?

On 2022-08-26 08:21:01, user Josh Atkins wrote:

Full article published at JNCI : https://doi.org/10.1093/jnc...

On 2022-10-20 16:49:56, user Stefan Heber wrote:

There is already an article published in a journal corresponding to this preprint:

On 2022-10-24 11:51:28, user Indi Trehan wrote:

This article has now been published after peer review: The Journal of Pediatrics 2022; 247: 147-149. doi: 10.1016/j.jpeds.2022.05.006.

On 2022-12-04 06:38:01, user Jianyu Lai wrote:

This manuscript is now published in Microbiology Spectrum. DOI: https://doi.org/10.1128/spe...

On 2023-04-12 16:21:36, user Lizeth Perales wrote:

Hello, I would love to get access to the data. Please let me know if that is possible! thank you in advance

On 2020-04-06 19:55:46, user Sinai Immunol Review Project wrote:

Clinical Characteristics of 2019 Novel Infected Coronavirus Pneumonia:A Systemic Review and Meta-analysis

The authors performed a meta analysis of literature on clinical, laboratory and radiologic characteristics of patients presenting with pneumonia related to SARSCoV2 infection, published up to Feb 6 2020. They found that symptoms that were mostly consistent among studies were sore throat, headache, diarrhea and rhinorrhea. Fever, cough, malaise and muscle pain were highly variable across studies. Leukopenia (mostly lymphocytopenia) and increased white blood cells were highly variable across studies. They identified three most common patterns seen on CT scan, but there was high variability across studies. Consistently across the studies examined, the authors found that about 75% of patients need supplemental oxygen therapy, about 23% mechanical ventilation and about 5% extracorporeal membrane oxygenation (ECMO). The authors calculated a staggering pooled mortality incidence of 78% for these patients.

Critical analysis:<br /> The authors mention that the total number of studies included in this meta analysis is nine, however they also mentioned that only three studies reported individual patient data. It is overall unclear how many patients in total were included in their analysis. This is mostly relevant as they reported an incredibly high mortality (78%) and mention an absolute number of deaths of 26 cases overall. It is not clear from their report how the mortality rate was calculated. <br /> The data is based on reports from China and mostly from the Wuhan area, which somewhat limits the overall generalizability and applicability of these results.

Importance and implications of these findings in the context of the current epidemics:<br /> This meta analysis offers some important data for clinicians to refer to when dealing with patients with COVID-19 and specifically with pneumonia. It is very helpful to set expectations about the course of the disease.

On 2020-06-01 16:23:11, user OxImmuno Literature Initiative wrote:

https://www.immunology.ox.a...

On 2023-09-22 06:06:43, user Anikó Lovik wrote:

This preprint has not been published in The Lancet Regional Health - Europe with DOI: https://doi.org/10.1016/j.l...<br /> Please read and cite the updated new version. Thank you.

On 2023-12-12 14:56:15, user Tanmoy Sarkar Pias wrote:

This paper has been accepted to an IEEE conference. A link (& DOI) to the IEEE Xplore will be added when this article is published. Please see the following copy right details of IEEE.

2023 26th International Conference on Computer and Information Technology (ICCIT), 13-15 December, Cox’s Bazar, Bangladesh

979-8-3503-5901-5/23/$31.00 ©2023 IEEE

On 2023-12-19 12:39:03, user Christos Proukakis wrote:

Response to: “Is Gauchian genotyping of GBA1 variants reliable?”

Marco Toffoli1,2, Anthony HV Schapira1,2, Fritz J Sedlazeck2,3,4, Christos Proukakis1,2 *

1. Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, UK
2. Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA
3. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA
4. Department of Molecular and Human Genetics, Baylor College of Medicine, TX, USA

* To whom correspondence should be addressed: c.proukakis@ucl.ac.uk

We recently described two methods for GBA1 analysis, which is hampered by the adjacent highly homologous pseudogene: Gauchian, a novel algorithm for analysis of short-read WGS, and targeted long-read sequencing 1. Tayebi et al have applied the former to WGS from 95 individuals, and compared it to Sanger sequencing 2. They report concordant genotypes in 85, while 11 had discrepant calls (we note that this leads to a total of 96). In addition, they report 28 false Gauchian calls in 1000 Genomes Project (1kGP) samples. Gauchian was developed because the homology of the GBA region requires a short read variant caller that does not rely solely on read alignments, and can identify specific variants known to be pathogenic. To understand the cause of these discrepancies, we reviewed their data, and conclude that they are mis-interpreting Gauchian results in 8 of the 11 discrepant samples, and incorrectly using Gauchian to analyze low-coverage 1kGP samples.

Among the 11 (11.5%) samples with inconsistent calls with Sanger (Table 1), four (Pat_08, Pat_26, Pat_28 and Pat_58) were not called as the variants are not on Gauchian’s target list, which includes all ClinVar variants in December 2021. These variants, and any others, can be easily added (see Supplementary Information). Three other samples (Pat_75, Pat_76 and Pat_79) had low data quality resulting in large variation in sequencing depth across the genome, as shown by the median absolute deviation (MAD) of genome coverage: 0.269, 0.128 and 0.127 (three highest values among all samples). Gauchian recommends trusting calls in samples with MAD values <0.11, and produces a warning message if this is exceeded. In all three samples, the GBA1+GBAP1 copy number was a no-call (marked as “None” in the output file), indicating that Gauchian could not determine the copy number due to high coverage variation. Variants were not called because no further analysis was done beyond copy number calling. These should not be viewed as false negatives, as the warning message and the report of no-calls should prompt the user to obtain higher quality data or consider alternative sequencing. Among the remaining 4 samples with inconsistent results: Pat_03 had a Gauchian call of heterozygosity for p.Asn409Ser, while Sanger reports this as homozygous. Review of the IGV trace (Tayebi et al. Supp Figure 1) shows that at least 10 reads (around a fifth of the total) have the reference base, and therefore it is hard to conclude this is homozygous. Review of the Sanger trace (not provided) could determine whether there is a low peak representing the reference allele. We cannot provide a conclusion, and additional analysis is recommended. Mosaicism could be a plausible explanation, and this has been reported in GBA1 3,4, albeit not at this position. Pat_47 had a false negative p.Leu483Pro call. Pat_16 was indeed wrongly genotyped as homozygous for p.Asn409Ser, related to the adjacent c.1263del+RecTL deletion. Pat_92 had all expected variants called, but the heterozygous p.Asp448His was mis-genotyped as homozygous. In summary, there is one false negative and two wrongly genotyped variants (heterozygous variants called homozygous). Gauchian’s precision is therefore 98.9% (175 out of 177 calls are correct). Its allele-level recall/sensitivity is 99.4% after excluding alleles not on Gauchian’s target list, and samples which could not be analyzed due to high coverage variation. Alternatively, it can be calculated as 97.2% if only samples with high coverage variation are excluded, 96.2% if only alleles not on the target list are excluded, and 94.1% if all these samples are considered .

Tayebi et al. concluded that Gauchian is not able to call recombinant variants without providing orthogonal evidence. In Pat_95, Pat_71 and Pat_16, they examined alignments in IGV and reported absence of supporting reads for Gauchian calls, but all recombinant alleles called by Gauchian were consistent with Sanger. This highlights that read mapping in this region is unreliable (variant supporting reads may align to the pseudogene), making interpretation of alignments in IGV very challenging. Gauchian is designed to untangle ambiguous alignments, locally phase haplotypes and make correct calls. Particularly, in Pat_95, they claimed that Gauchian called the expected RecNciI variant but got the mechanism of the recombinant allele wrong (gene conversion vs. gene fusion). This claim appears to be based on incorrect interpretation of IGV alignments, i.e. seeing 3’ UTR mismatches associated with GBAP1 does not necessarily indicate gene fusion, as they can be misalignments, or even part of the gene conversion. The RecNciI in Pat_95 is a gene conversion, as indicated by the normal copy number between GBAP1 and GBA1. Tayebi et al. claimed that this is a gene fusion without orthogonal evidence. In addition, they claimed that Gauchian misreported copy numbers in Pat_92, Pat_42 and Pat_72, again without orthogonal evidence. We validated Gauchian copy number gains by digital PCR in four cases 1. While particular recombinants could be prone to erroneous copy number calling, we do not know what “other techniques'' identified a different copy number in Pat_92. Orthogonal validation using digital PCR would resolve this. Finally, it is true that Gauchian does not have all possible recombinants on its target list, as it is designed to focus on recombinant variants in exons 9-11, because others are rare and detectable with standard callers.

Tayebi et al. reported 4 samples where Gauchian missed variants in GRCh38 compared to GRCh37. Among these, two (Pat_35, Pat_75) were due to incorrect alignment settings that resulted in abnormally low mapping quality throughout the region. It is likely that ALT-aware alignment was on for all samples except these two. The remaining two (Pat_16, Pat_78) reflected an area of improvement for Gauchian to better call p.Asn409Ser, which is not a GBAP1-like variant, and can thus be called well by standard callers.

We reported Gauchian calls of 1000 Genomes Project (1kGP) samples, validating some by targeted long reads 1. Gauchian called zero samples with biallelic variant in exons 9-11. However, Tayebi et al. reported a completely different set of Gauchian calls in the same samples (in their Table 4). This was caused by incorrect use of Gauchian on old low coverage WGS (median coverage <10X, https://ftp.1000genomes.ebi... "https://ftp.1000genomes.ebi.ac.uk/vol1/ftp/phase3/data/)"), rather than 30X (https://ftp-trace.ncbi.nlm.... "https://ftp-trace.ncbi.nlm.nih.gov/1000genomes/ftp/1000G_2504_high_coverage/data/)").

We are grateful to Tayebi et al for assessing Gauchian analysis of this very challenging gene 2, but note that most discrepancies were due to incorrect use or misinterpretation of results. “No call” samples due to inadequate data quality cannot be considered false negative, as no calls are provided, and warnings of noisy coverage are given where applicable. Samples with inadequate coverage should obviously be avoided, as Gauchian is expected to perform at coverage >30X. Gauchian does not call variants not on its target list, which can be expanded. We provide updated recall (99.4%) and precision (98.9%) values. We have not seen any evidence of the alleged inability of Gauchian to call recombinant variants, and would welcome orthogonal copy number assessment of discrepancies. We show that Gauchian can be used for GBA1 assessment when coverage and data quality are adequate. We do note a limitation in genotyping p.Asn409Ser, a non-recombinant variant that can be called by standard variant callers, which we recommend running together with Gauchian for a complete call set. Finally, in clinical cases where absolute certainty is required, Sanger sequencing could be considered, with targeted long read sequencing another option 1,5–7.

Table 1. Details on the 11 samples where Gauchian and Sanger are inconsistent.

Gauchian calls Sanger Assessment,Tayebi et al. Our assessmentSample Copy Number of GBA1 and GBAP1 GBAP1-like variant in exons 9-11 Other unphased variants Genotype Prediction

Pat_08 4 None p.Asn409Ser p.Asn409Ser/p.Gln389Ter False Negative Missed variant is not on Gauchian's target list

Pat_28 4 None p.Arg535His p.Arg535His/Cys381Tyr False Negative Missed variant is not on Gauchian's target list

Pat_58 4 None p.Asn409Ser, p.Arg296Ter p.Asn409Ser, p.Arg296Ter, c.203delC False Negative Missed variant is not on Gauchian's target list

Pat_26 4 None p.Asn409Ser p.Asn409Ser/p.Arg502Cys False Negative Missed variant is not on Gauchian's target list.

Tayebi et al.’s Supplementary Figure 1 shows no variant at p.Arg502Cys (c.1504C>T), but a different variant at the neighboring position, p.Arg502His (c.1505G>A), which is not on Gauchian's target list.

Pat_75 None (No Call) NA NA p.Arg502Cys/p.Arg159Trp Missed Copy number is a no-calldue to high variation in depth so no further variant calling was performed. Coverage MAD 0.269

Pat_76 None (No Call) NA NA p.Asn409Ser/p.Asn409Ser Missed Copy number is a no-call due to high variation in depth so no further variant calling was performed. Coverage MAD 0.128

Pat_79 None (No Call) NA NA p.Leu483Pro/p.Arg502Cys Missed Copy number is a no-call due to high variation in depth so no further variant calling was performed. Coverage MAD 0.127

Pat_03 4 None p.Asn409Ser p.Asn409Ser/p.Asn409Ser False Negative Gauchian call is supported by reads, see Tayebi et al.’s Supplementary Figure 1.

Pat_47 4 None p.Asn409Ser p.Asn409Ser/p.Leu483Pro False Negative True false negative

Pat_16 3 c.1263del+RecTL/ p.Asn409Ser, p.Asn409Ser p.Asn409Ser, c.1263del+RecTL False Positive Heterozygous p.Asn409Ser misgenotyped as homozygous as Gauchian did not know the exact breakpoint of the c.1263del+RecTL deletion, which is very close to p.Asn409Ser.

Pat_92 7 p.Asp448His/p.Leu483Pro,p.Asp448His p.Asp448His/ p.Leu483Pro+Rec7 False Negative There is no false negative. Rec7 is reflected in the copy number call (copy number gain). This GBAP1 duplication does not have any functional impact on GBA, so Gauchian does not report it as a GBA variant. Heterozygous p.Asp448His misgenotyped as homozygous.

Acknowledgements

We are grateful to Xiao Chen and Michael Eberle for helpful comments. They are former employees of Illumina and current employees of Pacific Biosciences. This research was funded in in part by Aligning Science Across Parkinson's [Grant numbers 000430 and 000420] through the Michael J. Fox Foundation for Parkinson's Research (MJFF).

Competing interests

FJS receives research support from PacBio and Oxford Nanopore. AHVS has received consulting fees from AvroBio, Auxilius, Coave, Destin, Enterin, Escape Bio, Genilac, and Sanofi and speaking fees from Prada Foundation.

Supplementary Information

Add new variants to Gauchian’s config file

The four new variants can be added to Gauchian’s config file as follows.

For hg38, add the following lines to gauchian/data/GBA_target_variant_38.txt

chr1 155236304 A GBAP G c.1165C>T(p.Gln389Ter)<br /> chr1 155236327 T GBAP C c.1142G>A(p.Cys381Tyr)<br /> chr1 155239989 CGGGGGT GBAP CGGGGGGT c.203delC(p.Thr69fs)

Add the following line to gauchian/data/GBA_target_variant_homology_region_38.txt<br /> chr1 155235195 T 155214568 C c.1505G>A(p.Arg502His)

For GRCh37, add the following lines to gauchian/data/GBA_target_variant_37.txt<br /> 1 155206095 A GBAP G c.1165C>T(p.Gln389Ter)<br /> 1 155206118 T GBAP C c.1142G>A(p.Cys381Tyr)<br /> 1 155209780 CGGGGGT GBAP CGGGGGGT c.203delC(p.Thr69fs)

Add the following line to gauchian/data/GBA_target_variant_homology_region_37.txt<br /> 1 155204986 T 155184359 C c.1505G>A(p.Arg502His)

Bibliography

1. Toffoli, M. et al. Comprehensive short and long read sequencing analysis for the Gaucher and Parkinson’s disease-associated GBA gene. Commun. Biol. 5, 670 (2022).

2. Tayebi, N., Lichtenberg, J., Hertz, E. & Sidransky, E. Is Gauchian genotyping of GBA1 variants reliable? medRxiv (2023) doi:10.1101/2023.10.26.23297627.

3. Filocamo, M. et al. Somatic mosaicism in a patient with Gaucher disease type 2: implication for genetic counseling and therapeutic decision-making. Blood Cells Mol. Dis. 26, 611–612 (2000).

4. Hagege, E. et al. Type 2 Gaucher disease in an infant despite a normal maternal glucocerebrosidase gene. Am. J. Med. Genet. A 173, 3211–3215 (2017).

5. Pachchek, S. et al. Accurate long-read sequencing identified GBA1 as major risk factor in the Luxembourgish Parkinson’s study. npj Parkinsons Disease 9, 156 (2023).

6. Graham, O. E. E. et al. Nanopore sequencing of the glucocerebrosidase (GBA) gene in a New Zealand Parkinson’s disease cohort. Parkinsonism Relat. Disord. 70, 36–41 (2020).

7. Leija-Salazar, M. et al. Evaluation of the detection of GBA missense mutations and other variants using the Oxford Nanopore MinION. Mol. Genet. Genomic Med. 7, e564 (2019)

On 2024-03-05 22:33:49, user Po-Kai Yang wrote:

Hi, I am the author of this preprint. The paper was published on https://jneuroengrehab.biom...

Could you make a link to the published version? Thank you!

On 2024-03-15 12:33:53, user Robin Walters wrote:

This is published, Nature Genetics 55,<br /> 410–422

On 2024-04-11 17:53:00, user eysen wrote:

JMIR Publications and PREreview are pleased to announce our next Preprint Live Review on Friday, April 19 at 9am PT / 12pm ET / 4pm UTC which discusses this preprint

Register Now at https://docs.google.com/for...

The Live Review is hosted by two facilitators from the PREreview team with experience in moderating virtual collaborative review discussions. They will guide participants through a constructive discussion of the following preprint: Assessing the Incidence of Postoperative Diabetes in Gastric Cancer Patients: A Comparative Study of Roux-en-Y Gastrectomy and Other Surgical Reconstruction Techniques - by Tatsuki Onishi

Live Review Details:

WHEN: Friday, April 19 at 9am PT / 12pm ET / 4pm UTC

WHO: The Live Review is hosted by two facilitators from the PREreview team with experience in moderating virtual collaborative review discussions.

WHAT: The participants will be guided through a constructive discussion of the following preprint: Assessing the Incidence of Postoperative Diabetes in Gastric Cancer Patients: A Comparative Study of Roux-en-Y Gastrectomy and Other Surgical Reconstruction Techniques - by Tatsuki Onishi medRxiv: https://doi.org/10.1101/202...

A review will be then written and published on PREreview.org within the following 2 weeks. Participants will have the chance to help compose the final review and be recognized as reviewing authors.

HOW: To participate, please complete the following registration form. You will receive an email from PREReview with a link to a Zoom room and a passcode.

More information on JMIRx-Med, the first pubmed-indexed preprint overlay journal: https://xmed.jmir.org/annou...<br /> https://xmed.jmir.org/announcements/457

On 2024-05-03 15:04:37, user Tamy wrote:

I am happy to see someone taking an interest in this horrific condition. My daughter has suffered for over 9 years and the mental toll, as well as, the physical toll it has taken on her overall well being has been life changing! Thank you for giving these sufferers some validation!

On 2020-08-24 17:31:53, user Mercer Creed wrote:

Where is the information regarding controls?

On 2025-03-09 21:02:55, user Dr. DP wrote:

Dear authors,<br /> Will this article be peer-reviewed/is there a path to peer-review being explored?

On 2025-05-01 12:48:20, user Ravi Sharma wrote:

Ladies and Gentlemen,

in loving memory of my late, beloved mother, a type 2 diabetic since my birth, I dedicate this research to harnessing the beneficial power of gen-AI to banish GDM from the face of the earth.

I salute my industrious and loyal research group for their dedication in this journey.

Until our work is published and linked to this DoI, kindly cite this preprint as ...

Edmund Evangelistaa, Fathima Rubab, Syed M. Salman Bukhari, Amril Nazir and Ravishankar Sharma. (2025). "Developing a GraphRAG-enabled local-LLM for Gestational Diabetes Mellitus." medRxiv preprint doi: https://medrxiv.org/cgi/content/short/2025.04.28.25326568v1

With kind regards and best wishes, Ravi

On 2022-01-27 21:10:24, user Siguna Mueller, PhD, PhD wrote:

I find it difficult to see how many individuals were in each group. I may, or may not, be able to guess some proportions. For instance, Fig. 4 suggests that there were not many in the booster group, if any at all. (This is because boosters obviously were only rolled out not too long ago). Is the small peak at approx. 35 days since injection attributable to the booster group? If so, this makes me wonder if they were sufficiently many to be statistically relevant. Again, I find it hard to infer exact numbers of participants in the different groups. This info would really be helpful. Thanks.

On 2022-02-14 04:09:55, user RBNZ wrote:

"The estimates are furthermore adjusted for vaccine status of the potential secondary case interacted with the household variant, and the vaccine status of the primary case. "

There is no information included as to how vaccination status adjusts the odds ratio.

On 2022-02-03 14:15:23, user Matt Thrun-Nowicki wrote:

Given previous studies’ evidence of a poor association between RAT results and viral culturability based on # of days after symptom onset, you guys might wanna wait to publish this paper until after those viral cultures result.

In addition, your explanation of why booster’d HCW had higher positive RAT’s is a little baffling. If your explanation was correct, wouldn’t you expect to see the percentage of positive RAT’s among booster’d HCWers drop over time, and those of unbooster’d go up? What about confounders (like demographics of the booster’d vs unbooster’d)?

On 2025-09-07 20:13:12, user S S Young wrote:

Milojevic et al. 2014 had access to all emergency room visits for all of England and Wales for the years 2003 to 2008, over 400,000 myocardial infarction (MI) events, and over 2 million CVD emergency hospital admissions. They found no effect of CO, NO2, Ozone, PM10, PM2.5, or SO2 on heart attacks, hospital admissions, or mortality, their Figures 1 and 2.

Milojevic, A., Wilkinson, P., Armstrong, B., Bhaskaran, K., Smeeth, L., Hajat, S. 2014. Short-term effects of air pollution on a range of cardiovascular events in England and Wales: Case-crossover analysis of the MINAP database, hospital admissions and mortality. Heart (British Cardiac Society) 100, 14: 1093-98. https://doi.org/10.1136/heartjnl-2013-304963 .

On 2022-02-03 18:10:45, user Rodrigo Zepeda wrote:

Methods equation 6. Y(t) is never defined. Is it the observed case count?

On 2022-02-07 10:26:48, user Daksya Siddhi wrote:

The article has now been published at<br /> https://journals.plos.org/p...

Supplemental data which includes tables on patient characteristics and D3 measurement is at<br /> https://app.dimensions.ai/d...

On 2020-04-19 16:51:41, user Sinai Immunol Review Project wrote:

Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications

Fan Wu et al.; medRxiv 2020.03.30.20047365; doi:https://doi.org/10.1101/202...

Keywords

• Neutralizing antibodies<br /> • SARS-CoV-2<br /> • pseudotype neutralization assay

Main findings

In this study, plasma obtained from 175 convalescent patients with laboratory-confirmed mild COVID-19 was screened for SARS-CoV-2-specific neutralizing antibodies (nABs) by pseudotype-lentiviral-vector-based neutralization assay as well as for binding antibodies (Abs) against SARS-CoV-2 RBD, S1 and S2 proteins by ELISA. Kinetics of neutralizing and binding Ab titers were assessed during the acute and convalescent phase in the context of patient age as well as in relation to clinical markers of inflammation (CRP and lymphocyte count at the time of hospitalization). Across all age groups, SARS-CoV-2-specific nAbs titers were low within the first 10 days of symptom onset, peaked between days 10-15, and persisted for at least two weeks post discharge. In contrast to spike protein binding Abs, nAbs were not cross-reactive to SARS-CoV-1. Moreover, nAb titers moderately correlated with the amount of spike protein binding antibodies. Both neutralizing and binding Ab titers varied across patient subsets of all ages, but were significantly higher in middle-aged (40-59 yrs) and elderly (60-85) vs. younger patients (15-39 yrs). However, plasma nAb titers were found to be below detection level in 5.7% (10/175) of patients, i.e. a small number of patients recovered without developing a robust nAb response. Conversely, 1.14% (2/175) of patients had substantially higher titers than the rest. Notably, in addition to patient age, nAb titers correlated moderately with serum CRP levels but were inversely related to lymphocyte count on admission. In summary, the authors show that patients with clinically mild COVID-19 disease mount a strong humoral response against the SARS-CoV-2 spike protein. Compared to younger patients, middle-aged and elderly patients had both higher neutralizing and binding Ab titers, accompanied by increased CRP levels and lower lymphocyte counts. These patients are usually considered at higher risk of severe disease. Therefore, robust neutralizing and binding Ab responses may be particularly important for recovery in this patient subset. Conversely, patients who failed to produce high nAb/binding Ab titers against spike protein did not progress to severe disease, indicating that binding Abs against other viral epitopes as well as cellular immune responses are equally important.

Limitations

This study provides valuable information on the kinetics of spike protein-specific nAb as well as binding Ab titers in a cohort of convalescent mild COVID-19 patients of all ages. However, similar studies enrolling larger patient numbers, including those diagnosed with moderate and severe disease as well as survivors and non-survivors, especially in the elderly group (to rule out potential bias for more favorable outcome), are warranted for reliable assumptions on the potentially protective role of Abs and nAbs in COVID-19. Moreover, longitudinal observation beyond the acute and convalescent phase in addition to stringent clinical and immunological characterization is urgently needed. <br /> In their study, Wu et al. did not measure binding Abs against non-S viral proteins, which are also induced in COVID-19 and therefore could have added valuable diagnostic information with regard to patients who seemingly failed to mount both binding and neutralizing Ab responses against the SARS-CoV-2 spike protein. Likewise, while this study excluded cross-reactivity of nAbs against SARS-CoV-1, no other coronaviruses were tested. Of additional note, neutralizing activity of plasma Abs was only assessed by pseudotype neutralization assay, not against live SARS-CoV-2. Generally, while these are widely used and reproducible assays, in vitro neutralization of pseudotyped viruses does not necessarily translate to effective protection against the respective live virus in vivo (cf. review by Burton, D. Antibodies, viruses and vaccines. Nat Rev Immunol 2, 706–713 (2002)). Further studies are therefore needed to assess the specificity and neutralizing characteristics of these Abs to test whether they could be candidates for prophylactic and therapeutic interventions. In this context, setting arbitrary cut-off values (ID50<500 vs. a detection limit of ID50 < 40) and thus classifying up to 30% of patients in this study as “weak” responders does not take into account our currently limited knowledge regarding protective capacity of these nAbs and should therefore have been avoided by the authors.

Significance

This preprint is arguably the first report on neutralizing and binding Ab titers in a larger cohort of mild COVID-19 patients. Assessing Ab titers in these patients is not only important in order to confirm whether mild COVID-19 elicits robust nAb responses, but also adds further information regarding the use of plasma from mild disease patients for convalescent plasma therapy as well as vaccine design in general. Future studies will need to address now whether the nAb responses generated in mild disease will be protective or (functionally) different from nAbs generated in moderate and severe disease. The findings in this study are therefore of great relevance and should be further explored in ongoing research on potential coronavirus therapies and prevention strategies.

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 2025-11-30 23:44:45, user Cyril Burke wrote:

[Note: This is the second of several rounds of review of an earlier version of our combined manuscript, aiming 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 included our responses, at the end of this comment. The changing title and line numbers refer to earlier versions.]

August 3, 2022<br /> Dear Dr. Burke III,

REDACTED.

Reviewer #1: Cyril O Burke III et al submit a revised version of their intriguing , unusual paper.

Overall, the paper remains extremely lengthy (the total , including clean and track versions and reply to reviewers is close to 200 pages !!) , whereas it contains relatively little original data.

The authors speculate and comment a lot (and most of these speculations/comments will hardly be understandable by the expected audience, primary care physicians), and this will in addition distract the reader from the main key message (which is right in the opinion of this reviewer (see first round of review) and warrants more attention and studies.

The race part is irrelevant for the key point (race does not change over time, and thus is not relevant when looking at longitudinal serum creatinine or eGFR) and should be deleted in the opinion of this reviewer. In this respect, I completely agree with the comment of reviewer 2 in the first round.

I can not resist quoting here the reply of the authors to reviewer 2. “This manuscript could be divided into three or four short papers, increasing the likelihood that any one of them would be read. However, different groups tend to read papers about screening for kidney impairment, racial disparities, cofactors in modeling physiologic parameters, or policy proposals to encourage best practices. Despite the appeal of perhaps three or four publications, we decided to tell a complete story in a single paper, but we are open to suggestions.”

My reply to their reply: nobody would read the current paper , even partially. Shorten, shorten, shorten please and focus on the key message.

Reviewer #2: Thank-you, once again, for the opportunity to review this lengthy “thesis-style” manuscript which discusses some important often over-looked topics. The under-use of serial creatinine measurements and over-reliance on often erroneous eGFR measurements is an important point which is easily missed by healthcare workers with potentially serious consequences. Likewise, the misuse of racial constructs in medicine (and elsewhere) is an important point.

I am satisfied with this re-submission and the changes which have been made to the original manuscript.

Minor points:<br /> 431: “creatinine inhibits several membrane transporters”. = Cimetidine

502: “Because mGFRs have population variation as wide as sCr, with much greater physiologic variability compared to the relatively stable sCr and serum cystatin C”<br /> As mentioned previously the cited article compares the variability of sCr and cystatin C with CrCl, I agree with the authors that CrCl is a form of mGFR, however, probably one of the poorer forms and not what a reader will think of when mGFR is mentioned. In our current age of medicine when we talk about mGFR CrCl is seldom included, studies reviewing methods of mGFR will seldom include CrCl, however CrCl may be compared to one of the mGFR methods. Likewise, if a patient is sent for a mGFR, a CrCl will not be performed. In our current age of medicine mGFR refers to methods such as the clearance of iohexol, iothalamate, Cr-EDTA, inulin, DTPA, etc; the authors themselves mention this (line 539 – 540). I fully agree with the authors that mGFR is FAR from perfect and has many inaccuracies and imprecisions (which are often overlooked)- these are well published, some of which are cited in this manuscript. If the authors wish to use the current study as a source they should state the findings in a way that cannot be misinterpreted. For example: “CrCl has much greater physiologic variability than sCr and cystatin C …” – in this case the reader can determine for themselves whether they would use CrCl as a surrogate for mGFR. Alternatively, adjust the statement and use another source which has shown the variability that exists with what we currently refer to as mGFR method.

670 – 719: As the authors specifically discuss age it would be prudent to briefly mention the short-comings, or considerations for interpretation, of serial creatinine measurements at a very young age which generally rise until late adolescence when steady muscle mass is achieved. Also note changes in creatinine and GFR from birth till 2 – 3 years.

783 – 784: Consider re-wording the grammar makes this sentence difficult to read

959 – 968: Note, editing has not been accepted (tracked changes still shown)

1116 - 1121: “Using the opioid crisis as an example…. in, for example, the opioid crisis” – same sentence

RESPONSE TO REVIEWERS:<br /> September 17, 2022<br /> Longitudinal creatinine, not ‘race’, signals pre-chronic kidney disease and decline in glomerular filtration rate

We again greatly appreciate the reviewers for offering detailed comments and guidance, which we have endeavored to incorporate as best we could.

Comments to the Author<br /> Reviewer #1: Cyril O Burke III et al submit a revised version of their intriguing, unusual paper.<br /> 1. Overall, the paper remains extremely lengthy (the total, including clean and track versions and reply to reviewers is close to 200 pages !!), whereas it contains relatively little original data.<br /> The authors speculate and comment a lot (and most of these speculations/comments will hardly be understandable by the expected audience, primary care physicians), and this will in addition distract the reader from the main key message (which is right in the opinion of this reviewer (see first round of review) and warrants more attention and studies.<br /> The race part is irrelevant for the key point (race does not change over time, and thus is not relevant when looking at longitudinal serum creatinine or eGFR) and should be deleted in the opinion of this reviewer. In this respect, I completely agree with the comment of reviewer 2 in the first round.<br /> I can not resist quoting here the reply of the authors to reviewer 2.<br /> "This manuscript could be divided into three or four short papers, increasing the likelihood that any one of them would be read. However, different groups tend to read papers about screening for kidney impairment, racial disparities, cofactors in modeling physiologic parameters, or policy proposals to encourage best practices. Despite the appeal of perhaps three or four publications, we decided to tell a complete story in a single paper, but we are open to suggestions."<br /> My reply to their reply: nobody would read the current paper, even partially. Shorten, shorten, shorten please, and focus on the key message.<br /> We fundamentally agree and have worked to shorten the text; to clarify our understanding that ‘race’ may change with time, location, and self-identification; and to add a Table of Contents to make the Parts more accessible to interested readers. We comment a lot because, in highly racialized societies, like the US [1,2], it can be difficult to see beyond ‘race’ without explicit speculation about other possible explanations for difference, which we understand, may or may not pan out under investigation. One hope is that all clinicians will pursue explanations other than ‘race’, but this seems unlikely. Busy medical researchers have little time to develop expertise outside their area of interest, which may explain why ‘Commentary’ and ‘Perspective’ articles have failed to inspire an ethical ban on the misuse of ‘race’ in medical research, journals, clinics, and elsewhere [3]. We do not know whether a suite of articles can meaningfully contribute to ending misuse of ‘race’, where so many scholarly articles have failed, but after perceiving little change over four decades, trying something completely different seemed (almost) rational.

1. Nunez-Smith M, Curry LA, Bigby J, Berg D, Krumholz HM, Bradley EH. Impact of race on the professional lives of physicians of African descent. Ann Intern Med. 2007 Jan 2;146(1):45-51. doi: 10.7326/0003-4819-146-1-200701020-00008. PMID: 17200221.

2. Betancourt JR, Reid AE. Black physicians' experience with race: should we be surprised? Ann Intern Med. 2007 Jan 2;146(1):68-9. doi: 10.7326/0003-4819-146-1-200701020-00013. PMID: 17200226.

3. McFarling UL. Troubling podcast puts JAMA, the ‘voice of medicine,’ under fire for its mishandling of race. Stat News. 2021 April 6 [Cited 2022 August 31]. Available from: https://www.statnews.com/2021/04/06/podcast-puts-jama-under-fire-for-mishandling-of-race/ <br /> Reviewer #2: Thank-you, once again, for the opportunity to review this lengthy “thesis-style” manuscript which discusses some important often over-looked topics. The under-use of serial creatinine measurements and over-reliance on often erroneous eGFR measurements is an important point which is easily missed by healthcare workers with potentially serious consequences. Likewise, the misuse of racial constructs in medicine (and elsewhere) is an important point.<br /> Thank you for again giving time for helpful criticism and comments on our manuscript.

A. I am satisfied with this re-submission and the changes which have been made to the original manuscript.<br /> Minor points:<br /> B. 431: “creatinine inhibits several membrane transporters”. = Cimetidine<br /> Corrected.

C. 502: “Because mGFRs have population variation as wide as sCr, with much greater physiologic variability compared to the relatively stable sCr and serum cystatin C”<br /> As mentioned previously the cited article compares the variability of sCr and cystatin C with CrCl, I agree with the authors that CrCl is a form of mGFR, however, probably one of the poorer forms and not what a reader will think of when mGFR is mentioned. In our current age of medicine when we talk about mGFR CrCl is seldom included, studies reviewing methods of mGFR will seldom include CrCl, however CrCl may be compared to one of the mGFR methods. Likewise, if a patient is sent for a mGFR, a CrCl will not be performed. In our current age of medicine mGFR refers to methods such as the clearance of iohexol, iothalamate, Cr-EDTA, inulin, DTPA, etc; the authors themselves mention this (line 539 – 540). I fully agree with the authors that mGFR is FAR from perfect and has many inaccuracies and imprecisions (which are often overlooked)- these are well published, some of which are cited in this manuscript. If the authors wish to use the current study as a source they should state the findings in a way that cannot be misinterpreted. For example: “CrCl has much greater physiologic variability than sCr and cystatin C …” – in this case the reader can determine for themselves whether they would use CrCl as a surrogate for mGFR. Alternatively, adjust the statement and use another source which has shown the variability that exists with what we currently refer to as mGFR method.<br /> We appreciate this comment and have both added another reference and added to the text an argument for reconsidering creatinine clearance. Many hospitals and some countries lack the resources for advanced mGFR filtration markers, which are only used for research or for screening related to kidney transplants. However, most laboratories have the tools for ‘quick-creatinine clearance’ (quick-CrCl), which may be an acceptable alternative to the classic mGFRs. If confirmed, a simple and affordable quick-CrCl might allow hospitals and laboratories worldwide an alternative measurement requiring fewer assumptions for another aspect of glomerular filtration.

D. 670 – 719: As the authors specifically discuss age it would be prudent to briefly mention the short-comings, or considerations for interpretation, of serial creatinine measurements at a very young age which generally rise until late adolescence when steady muscle mass is achieved. Also note changes in creatinine and GFR from birth till 2 – 3 years.<br /> We have added a brief discussion of the diagnosis of CKD in infants, children, and adolescents.

E. 783 – 784: Consider re-wording, the grammar makes this sentence difficult to read<br /> Done.

F. 959 – 968: Note, editing has not been accepted (tracked changes still shown).<br /> Done.

G. 1116 - 1121: “Using the opioid crisis as an example…. in, for example, the opioid crisis” – same sentence.<br /> Rewritten.

We thank you.

On 2022-03-01 05:15:31, user Nun Daled Yud wrote:

clearly serial daily or twice daily testing is needed for patients who would benefit from the early antiviral treatments particularly aged care facilities .

On 2022-03-02 17:16:42, user HF wrote:

Is there any SPSS, Strata or R code available to replicate this project?

On 2022-03-09 02:39:17, user Peter J. Yim wrote:

Vaccine efficacy based on vaccination registries is dependent on the completeness of the registries. Any missing or improperly registered data contributes to misclassification bias: https://drive.google.com/fi...<br /> This study relies on the Citywide Immunization Registry (CIR) and the NYS Immunization Information System (NYSIIS). However, no evidence is presented for the accuracy of those registries. As such, the VE estimates from this study should be regarded as uncertain.

On 2022-05-05 12:39:51, user Robert Clark wrote:

The data shows efficacy against infection becomes NEGATIVE after one month. Imperative to found out if at longer times this also happens for hosp./deaths. Review the data to found out.

Robert Clark

On 2022-03-14 13:57:25, user SleepRhythm wrote:

This paper is now in press in Frontiers in Neuroscience - section Sleep and Circadian Rhythms: https://www.frontiersin.org...<br /> The medRxiv link will be forthcoming

On 2022-03-23 02:12:03, user Guest wrote:

Hello authors,<br /> Thank you for submitting a preprint of this interesting study on the virome to a public domain. I have a few questions regarding your methods and materials.<br /> First, the detailed description of sample collection was great, but I could not find any internal standards for the PCR steps, DNA extraction, or isolation of VLP. These might have been stated, somewhere else perhaps, but I could not identify them. However, for sample collection, how did you determine the location and type of wounds that would be tested? Was there a specific location or depth for chosen wounds or just all types stated that were within the frames of the criteria?<br /> Secondly, the methods for sample processing and DNA extraction are excellent, but I cannot seem to find any information regarding the primers used or the number of cycles performed while analyzing 16S rRNA. I could not find the total number of sequences obtained per sample, however, the quality reading for the viral reads was in-depth and well covered. I did not find any profile or 16S normalization or a total quantification of bacterial or bacterial numbers (like qPCR).<br /> Thirdly, I did not find anything about OTU abundance corrected for variance in copy numbers or variance in genome size. I also could not find any method details regarding coverage of communities measured or if there was any comparison to the dominate to rare. One last question, what do you define as ‘deep sequencing’ regarding this study?<br /> Overall, I found this article very interesting and a good read. Thank you for providing such excellent work with the virome. I have not seen many studies regarding the effects of the virome on human healing, host interactions, or composition until recent years, but this article provides a great starting point for these types of studies.

SHSU5394

On 2022-04-07 15:07:03, user Addi Romero wrote:

A revised, updated version has been published as a correspondence in The Lancet Infectious Diseases. A link will be forthcoming. Meanwhile, feel free to have a look at the In Press, Corrected Proof: <br /> https://www.sciencedirect.c...

Dynamics of humoral and T-cell immunity after three BNT162b2 vaccinations in adults older than 80 years

On 2022-04-13 12:35:52, user Josué OUEDRAOGO wrote:

Hello! Thank you for this work.<br /> How can i get your dataset?

On 2022-04-23 17:06:25, user Ozzy96 wrote:

What is the all cause <br /> background rate of myocarditis in this age group pre-covid??

On 2022-04-25 13:00:30, user Sakari Jukarainen wrote:

Thank you for pointing this out, it is indeed an error, to be fixed in the next version of this work.

On 2022-04-29 17:03:47, user Madhava Setty, MD wrote:

Very interesting study. From where did the data on viral copies come from? Also, the odds of seroconversion in placebo vs treatment, stated as 13.67 at a given viral copy level, doesn't seem to be reflected in the corresponding plot (B).

On 2022-05-06 12:44:06, user Showme wrote:

Any info about the peer reviewing progress?

On 2022-05-10 08:12:41, user Zeng Zhiyu wrote:

Figure 2. All 1 dose vs none, the dot is way greater than 1, why the OR is still 0.566?

On 2022-05-21 01:10:31, user Fritz Stumpges wrote:

You need to provide ground level readings for this test, for your group (1) without masks. Without this base, we don't know if your methods are just producing extremely high readings across the board!

On 2022-05-30 22:36:58, user Stuart Turville wrote:

Now published within this manuscript here:

Congratulations<br /> Dear Stuart G. Turville

We are pleased to inform you that your article has just been published:

Title<br /> Platform for isolation and characterization of SARS-CoV-2 variants enables rapid characterization of Omicron in Australia

Journal<br /> Nature Microbiology

DOI<br /> 10.1038/s41564-022-01135-7

Publication Date<br /> 2022-05-30

Your article is available online here https://doi.org/10.1038/s41... or as a PDF here https://www.nature.com/arti....

On 2022-06-03 06:08:07, user Toby Mansell wrote:

This paper has now been published at eLife. You can view the published version of this paper at: https://doi.org/10.7554/eLi...

On 2020-05-20 00:33:44, user SizzMo wrote:

It appears that the methods of administration of hydroxychloroquine were doomed to fail before even being undertaken. A review of the full study reveals NO mention of zinc, and suggests that hydroxychloroquine was administered alone or sometimes in tandem with azithromycin, and primarily to hospitalized patients in very late stages of illness. The omission of zinc and administration only in late stages of disease defeat the mechanism of action by which the hydroxychloroquine protocol works

The primary mechanism of action in the hydroxychloroquine+zinc+azithromycin protocol uses hydroxychloroquine primarily as an ionophore for zinc, which then inhibits viral replication in the cell cytoplasm. Zinc is an essential component of this protocol, and omitting zinc appears to be a fatal flaw in all of the reviewed studies and case reports in this analysis. Furthermore, this paper repeatedly refers to hydroxychloroquine being administered to hospitalized patients. The mechanism of action is the inhibition of viral replication, which reduces viral load at early stages of disease. Giving this protocol in late stages of disease when viral load is already heavy and patients are already severely ill defeats the purpose of the protocol and practically guarantees that it will not be effective. The methods reviewed in this study overlook what is known about both the mechanism of action of viral inibitors, and the synergistic function of hydroxychloroquine and zinc in viral RNA replication, making it appear that these "studies" were designed to fail.

Clinicians employing the complete hydroxychloroquine+zinc+azithromycin protocol at early stages of disease (mild to moderate illness) are universally reporting high levels of efficacy. <br /> Additionally, researchers in an NYU Langone retrospective analysis of more than 900 patients with mild-to-moderate illness who received the protocol with or without zinc also reported significant improvements in patients who received zinc. The NYU Langone study is currently undergoing peer review, and is available at this link: https://www.medrxiv.org/con...

On 2022-06-10 15:22:41, user Tammi Kral wrote:

The published version of this manuscript can be found in Science Advances at the following DOI:<br /> https://www.science.org/doi...

On 2022-07-18 12:29:27, user Loretta Lorenz wrote:

Quite likely many person are vaccinated and infected in various sequences. My question is, if the SARS-CoV 2 Spike protein measurement differentiated beetween spike proteins originating from a vaccine against COVID-19 and the different Spike Proteins of the various SARS-CoV-2 mutations.

On 2022-07-20 16:59:17, user Tania Watts wrote:

The authors may want to note similar findings in our paper, Dayam et al. Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases, JCI Insight, 10.1172/jci.insight.159721 April 2022. We show anti-TNF treated patients have lower Ab responses, no neutralization of Omicron and enhanced waning of T and Ab responses to SARS-CoV-2 mRNA vaccines after 2 doses.

On 2022-07-25 16:31:06, user Dr. D. Miyazawa MD wrote:

Please also refer to previous studies.

Hypothesis that hepatitis of unknown cause in children is caused by adeno-associated virus type 2 (08 May 2022)<br /> https://www.bmj.com/content...

Daisuke Miyazawa. Possible mechanisms for the hypothesis that acute hepatitis of unknown origin in children is caused by adeno-associated virus type 2. Authorea. May 16, 2022.<br /> DOI: 10.22541/au.165271065.53550386/v2

On 2022-07-28 17:24:57, user Mike Knudson wrote:

This paper is now published online in Transfusion.<br /> https://onlinelibrary.wiley...<br /> Major change was to add the results of eluate studies in the patients with a positive DAT following a transfusion reaction.

On 2022-07-29 13:52:30, user Stuart MacGowan wrote:

This is great work! A few years ago I worked on something similar - mapping missense variants to Pfams and defining constrained positions https://doi.org/10.1101/127050 . We also saw enrichment of pathogenic variants at constrained positions. Great to see this area moving forward!

On 2022-08-04 17:25:32, user Paul Hunter wrote:

Did you include date or week number in your model? During the study period there was a dramatic shift in the proportion of tests positive in Portugal from about 1 in 4.5 to 1 in 2 and that could explain your findings of a 3 x greater risk of hospitalisation associated with BA.5 infection irrespective of the actual risk . If you did not include week number then I think your conclusions are probably flawed.

On 2022-08-12 16:16:31, user A. M. Baxter wrote:

Alisdair Munro posted on Substack about this particular paper. It is an example of junk science spreading due to confirmation bias.

https://alasdairmunro.substack.com/p/how-junk-science-got-spread-like

"To put it bluntly, the results of this study are of no use at all. It is completely uninformative and would not pass as an undergraduate medical student assignment."

On 2022-09-28 17:51:37, user Jorge Cruz wrote:

This paper has now been published in Ann Clin Lab Sci July-August 2022 vol. 52 no. 4 651-662

On 2022-10-05 13:49:05, user Merja Rantala wrote:

Congrats for this preprint, it is an important summary what we know about protection of hybrid immunity and prior infection against cov19. However, I think that references and claims in the discussion should be checked. There was a sentence on page 13, first paragraph, claiming that covid survivors would have higher risk for dementia in addition to some other conditions. The reference cited was 36, which is not at all about risks for diseases after covid, but the other way around: risk factors for a severe covid outcome. So the ref need to be replaced. Moreover, we really don''t know at this stage whether risk for dementia is increased after covid or not, although has been under heavy speculation.

On 2020-05-26 23:26:41, user Sam Wheeler wrote:

The medical staff can get the virus while commuting to work. Especially if you work place is the place where patients go for covid testing or treatment, so you share the bus or subway with sick patients.

On 2020-05-27 01:37:02, user Keith wrote:

Very exciting new and a likely game changer for dentists/ENTs or anyone who manipulates the mucosa of a potentially covid + patient

On 2020-04-24 20:01:13, user Christos Ouzounis wrote:

Nice follow up from https://osf.io/397yg/

On 2024-01-18 15:30:55, user Brian Allan wrote:

This manuscript is now published in PLoS NTD:

https://doi.org/10.1371/jou...

On 2024-10-09 13:29:30, user disqus_foVd2sEK3I wrote:

Really nice work. Could you please share the accompanying code to reproduce these results? Thanks.

On 2025-04-10 17:31:51, user SMR Hashemian wrote:

At the peak of the COVID-19 crisis, when the world was gripped by fear and despair, Iran was not only battling a deadly virus but also grappling with brutal and inhumane sanctions. Economic sanctions severely restricted Iran's access to medicine, medical equipment, and vaccines, creating one of the biggest obstacles in the fight against this crisis. Yet, despite these unprecedented pressures, Iran did not surrender and, through relentless efforts, found ways to overcome these limitations.<br /> The Iranian government made every effort to bypass the sanctions through international negotiations and the creation of alternative financial channels to import the necessary medicines and equipment. These efforts, though fraught with difficulties, demonstrated Iran's resolve to save lives. Even as many countries refused to assist Iran, the nation relied on domestic capabilities and national solidarity to find solutions to the crisis.<br /> Amidst these challenges, Iran's healthcare workers stood on the front lines like unsung soldiers, making unparalleled sacrifices. Doctors, nurses, and all healthcare workers in hospitals not only played a critical role in saving countless lives but also faced significant personal risks, with many losing their lives in the process. These dedicated professionals demonstrated extraordinary commitment and selflessness, setting an example of resilience and dedication in the face of a global health crisis.<br /> But it was not just the healthcare workers who fought in this battle. Iran's scientific community also stepped up with full force. Iranian scientists and researchers, despite cruel sanctions and countless limitations, never stopped striving. They not only succeeded in producing domestic vaccines like Noora and SpikoGen, but also published numerous articles in prestigious international journals, showcasing Iran's role in advancing global science. These efforts are a testament to the fact that Iran, even under the toughest conditions, can rely on science and knowledge.<br /> The Iranian government, despite all limitations, spared no effort in controlling this crisis. From the very beginning, extensive education on health protocols was launched through the media. The public was continuously informed about health recommendations such as mask-wearing, social distancing, and hand hygiene. Even during Nowruz, one of the most important cultural events in Iran, the government encouraged people to reduce travel and celebrate at home. School and university closures, the shift to remote learning, and the reduction of workplace presence through teleworking all demonstrated the government's resolve to control the spread of the virus.<br /> These efforts, though accompanied by challenges, reflect Iran's national determination to confront this global crisis. Iran, despite all limitations, proved that it could stand firm against the toughest conditions by relying on science, sacrifice, and national solidarity. The accusations raised in this article are not only unfair but also overlook the relentless efforts of a nation. Iran fought with all its might to save lives, and that is something to be proud of.

Seyed MohammadReza Hashemian<br /> Professor of Critical Care Medicine

On 2020-05-06 21:53:31, user laurent moulin wrote:

Looks very interesting. Small Typo on figure 3 (I Guess...) with inversion of case and death on the France panel.

On 2020-04-20 15:36:38, user Philip Davies wrote:

Interesting study, thank you.

This is another study that attempts to ascertain if oral HCQ tablets can be of clinical use in patients more than one week into symptomatic disease, hospitalized with bilateral pneumonia and with evidence of established inflammatory reaction (cytokine storm). That's a big ask for any oral medication.

The study is again small (both arms have less than 100 patients). The most significant outcome measured (death) is realized in very small numbers (3 and 4). The confidence levels are extremely wide.

The are several problems with this study. There are marked differences in the two populations. The study honestly attempts to accommodate these confounding factors using a propensity score method (IPTW). Normally this method is valuable but here I can’t see that it has been well applied.

It pays to look at the raw data. There is a significant difference (between the two arms) in the initial intensity of disease.

At baseline (admission), HCQ arm comprises 78.3% men (>20% more of these higher risk patients than control arm with 64.9%); HCQ arm has 21.9% patients with more severe disease in the form of CT showing >50% lung affected). This is >80% more than in control arm (12.1%). HCQ arm has 90.5% patients with CRP > 40mg/l (CRP is a good indicator of impending/current severity). This is 10% higher than control arm (81.9%). HCQ arm had median O2 flow on admission = 3 litres/minute (50% higher than control arm at 2 litres / minute).

So, at baseline, the HCQ arm had significantly more patients with severe disease than control arm. The O2 flow is actually more significant than first sight would suggest. 2 l/m is always the first step in O2 therapy. The data shows us that most patients in the control arm could hold their sats on this first step therapy. This also means they may have been OK on just 1 l/m. We don't know. But we do know that most patients in the HQN could not hold their sats at that first step and needed an increase (3 l/m ... so that's 50-300% more O2 than control arm).

Admittedly there were other confounding factors which compromised the control arm more than HCQ arm (some chronic disease elements). But it's clear to me that disease severity was markedly more established in the HCQ arm.

Another factor to note: the HCQ treatment was not initiated at the moment those baseline values were obtained (on admission). The HCQ was initiated within 48 hours. So let’s look again at the timelines. The median duration of symptoms at admission shows that the HCQ arm comprised patients who were further into worsening illness: they were admitted on D8 compared to control, D7. They may not have had HCQ initiated until D10.

Then we look at outcomes: the raw data shows that the disadvantaged HCQ arm actually does better in the two most important outcomes, death and ICU admission. The HCQ delivers 12% less death and ICU admissions than the control arm. Admittedly the numbers are small so the confidence levels are very wide.

So what does that tell us? The answer is not much. But even accepting the poorly aligned baseline for disease severity, the outcomes with their wide 95% confidence levels do deliver a mildly promising indication on the 'swingometer'. They point more towards benefit than harm when using HCQ in this advanced disease state.

As a final comment on significant side effects (increased QT interval) from the use of HCQ. Once again, this trial used a particularly high dose of HCQ (600mg/day...right at ceiling dose for rheumatological use and much higher than the total antimalarial treatment dose). They also added azithromycin (another QT lengthening drug) to 20% of the HCQ patients. It’s not surprising at all to find such QT lengthening in a sick, more elderly population taking these medications in particularly high doses).

Further trials should utilize conservative doses of CQ/HCQ which have been proven safe in many millions of patients.

We don't yet know how this will pan out. We urgently need proper evidence. Statistically robust studies into prophylaxis and early intervention are likely to deliver the most interesting results.

Dr Philip Davies<br /> Aldershot Centre For Health<br /> http://thevirus.uk

On 2022-12-04 10:47:01, user Andronikos Koutroumpelis wrote:

The correlation between COVID and RSV history in patient-level data is interesting, but confounded by the very different characteristics of the subgroups (eg SES, age, race). Could the authors report a multivariate analysis to check if the two histories are correlated independently?

On 2021-05-26 15:18:37, user Turki Bin Hammad wrote:

The Astrazenca vaccine is reported to elicit much higher immune response when the second dose is given 2 to 3 months later compared to the 4-Week interval. Was the immune data for the AZD/Oxford vaccine in this study took into account the expected difference with various dosing schedules?

On 2020-12-02 03:08:13, user Kevin M wrote:

my wife runs an in home day care. We have 5 to 7 toddlers/infants per day. Some days she has a staff member. Children are with us 9.5 hours a day.

It is impossible to keep 2 & 3 year olds 6 feet away. Also to try to have them wear a mask, presents major choking hazards.

So based on these models, and i played around with Coarse Cotton, and Face Shield / No Mask. for the 5 people would be 27 minutes and 10 people 17m. Is that referencing Close contact, less than 6 feet?

Below those numbers it says 11 people can stay 6 feet apart indefinite... And on that i used Face Shield, 0% for Efficiency.

My thoughts are, having the same group of children here 9+ hours a day. With or without a mask/shield it doesnt matter?

And if maybe i had adults around and we had 6... 8..10 feet distance and no mask we are at a very low risk? Base on the "Note the six-foot or two meter...

I know this is not a 100% guide. But what are your thoughts on my scenarios?

On 2023-01-10 21:19:28, user Lucija Romac wrote:

Dear Authors,<br /> congratulations on the great work, I believe that your study is a huge step forward in the treatment of patients suffering from azoospermia and that every embryologist working with NOA and OA patients would be delighted to implement a non-invasive test, such as yours, in their lab. If you don't mind, I have a few questions. You stated that the NOA group included men with azoospermia confirmed by semen analysis and elevated FSH, (>18 IU/L) or by testicular biopsy. My question concerns the flow cytometry identification of morphologically intact AKAP4+/ASPX+/Hoechst+ spermatozoa in NOA semen pellets. I wonder whether the NOA mTESE reference set of 7 patients (Table 2) with the known mTESE outcome underwent histological evaluation which is known as the “gold standard” of diagnostic tools used to confirm the presence of spermatozoa in testicular tissue? I'm also curious why is the reference set comprised of only 7 patients, considering you had 91 NOA patients with a known outcome of mTESE?<br /> Thank you for your answers and for sharing your work with us,<br /> Best regards,<br /> Lucija Romac

On 2021-08-12 10:05:30, user Ken Sprenger wrote:

There are a number of concerns with the methodology and consistency in this study:<br /> 1. There is inconsistency in the description of the population of patients to be enrolled. The study registered on ClinicalTrials.gov (NCT 044297411) indicates that the study would include patients with mild to moderate COVID-19, whereas the title of the study published on medRxiv indicates that patients would have mild COVID-19. Then under Study Design in Methods in the publication, it indicates that the study would include mild to moderate COVID-19 patients. Then under Study Population in the publication it includes “asymptomatic cases”. In Table 1 All patients (N=89) and Symptomatic =72, therefore 17 (19%) of patients were asymptomatic. It would appear, therefore, that the definition of the study population had been substantially amended to include asymptomatic patients. There are a number of considerations:<br /> a. This was therefore no longer a study of ivermectin in patients with mild to moderate or even mild COVID-19, as stated in the publication and elsewhere.<br /> b. It would be important to know when the decision was made to enrol the asymptomatic patients and the reasons for this change.

1. Under Intervention in the Methods section of the publication, the authors say “Unexpectedly some patients who were isolated in the hotels as verified positive patients were found to be borderline or negative upon our RT-PCR test” and were withdrawn from the study. Figure 1 indicates that 7 patients assigned to the ivermectin arm and 14 patients assigned to the placebo arm had Ct values >35 in the “two first tests”. <br /> a. This means that 18% of patients were withdrawn after the start of the study as they had all been enrolled and randomized. <br /> b. The Ct values given in Figure 1 are all >35, and so it is difficult to understand why the text in the publication says “borderline or negative”. What did borderline mean in regard to Ct values? <br /> c. The authors state under Intervention in Methods that “… all RT-PCR tests, including verification that patients were positive on day zero, were conducted by the same lab, at the Israel Central Virology Laboratory of the Ministry Of Health (located at Sheba Medical Centre).”<br /> d. Withdrawing 18% of patients who initially qualified for the study (Ct confirmed by Ministry of Health laboratory) because they had reduced viral shedding (even if negative or approaching negative) in subsequent RT-PCR tests when reduction of viral shedding is the endpoint of the study, is problematic. Generally once patients are enrolled in a study they should not be withdrawn by the investigator except for safety reasons, or if the participant withdraws consent. An intention to treat analysis including these patients should have been performed.

2. There is a further change to the protocol which defines the time from symptom onset to start of medication. Initially start of study drug dosing appears to have been within 3 days of symptom onset, but then because of “delay in getting results in the community” of the RT-PCR this time was increased to 7 days from symptom onset. <br /> a. There is no indication of when this amendment was introduced, but it appears to be after the start of the study, in which case some patient’s day 6 (3 days from symptom onset + 3 days of study drug), will be different to others which will be 7 days from symptoms + 3 days of study drug. <br /> b. As it is possible that the viral load will be a little lower in patients on day 7 compared to day 3 after symptom onset, and the patients who started treatment on day 7 might reach Ct >30 at the end of 3 days of treatment sooner than patients who started treatment on day 3. <br /> c. Measuring the endpoint Ct (which will be changing with time, unrelated to study drug) at different intervals from baseline is potentially introducing a bias.

3. Medication is described differently in 3 places:<br /> a. Abstract in the publication: 0.2 mg/kg x 3 days.<br /> b. Randomisation section in Methods in the publication: in patients 40-69kg, 4 tablets (=12 mg daily) x 3 days and in patients >= 70 kg, 5 tablets (=15 mg daily) x 3 days.<br /> c. ClinicalTrials.com description: 3mg capsules, 15-20mg/day x 3 days.<br /> These three statements are all different doses and some are described as capsules, others as tablets. Consistency and the correct description of study medication is critical in a study which tests a drug against a placebo.

4. Primary outcome. Under Outcomes in the publication it states “The primary endpoint was viral clearance following a diagnostic swab taken on the sixth day (third day after termination of treatment), in the intervention group compared to placebo.” A negative swab was defined as RT-PCR Ct >30. The authors point out that the standard for a negative swab in Israel is a Ct >40 and, although they don’t mention this, the manufacturer of the RT-PCR kit used in the study (Seegene Allplex CoV19) recommends a cut-off Ct >40 in their manual. Despite these exiting standards they made a decision to use a Ct >30 because for a Ct >40 “reaching this level may take a few weeks, and there is significant evidence that a non-infectious state is usually achieved at Ct level >30”. <br /> a. It seems inappropriate in a study such as this, to change a commonly accepted standard (Ct >40) in Israel to save a “few weeks” of time. <br /> b. The point at which the decision was made to use the Ct >30 as negative is not declared and one would be concerned if it was taken after the start of the study and particularly if it was after unblinding of the study!

Conclusions:<br /> 1. There are numerous deviations from the ClinicalTrials.Gov description (amended version June 14, 2020) including: patient inclusion criteria, participant eligibility period post exposure (maximum 72 hours), study medication description, another 2 outcome measures which were not reported. Many deviations such as these raise concerns about the thoroughness with which the study was conducted and reported.<br /> 2. This was not a study of patients with mild to moderate COVID-19 as indicated in the publication title (or even with just mild COVID-19) as nearly 1 in 5 of randomized patients were asymptomatic. <br /> 3. A large number of patients (18%) were withdrawn from the study by the investigator as their RT-PCRs had Ct values >35) on day 2 and 4, after an initial positive. This is highly unusual and could have biased the study. An intention to treat analysis should have been performed. <br /> 4. The definition of a negative swab, which was really the endpoint, appears to have been made arbitrarily, as it did not align with Israel’s standards and the kit manufacturer’s manual, and there is no clarity as to when this decision was made. <br /> 5. A study amendment to the protocol which defined the time from symptom onset to start of study drug dosing was changed from 3 to 7 days. This could have biased the study.

It might be true that Ivermectin does reduce viral shedding time in mild to moderate COVID-19. However this study is not rigorous enough, includes amendments which could have introduced bias, and has methodological issues. In my opinion it should not be accepted as good evidence that ivermectin reduces viral loads and could reduce isolation time in patients with COVID-19.

On 2021-09-13 12:12:16, user Patrick Hunziker wrote:

Interesting paper.<br /> Might be useful to discuss it in the light of<br /> https://doi.org/10.33218/00...<br /> and<br /> https://ssrn.com/abstract=3...

On 2021-12-13 18:41:26, user Rogelio Martinez wrote:

Dr. Deoni,

Any thoughts regarding possibility of increased lead exposure? Although, if lead was a main driving factor one would have thought the effects would have been worse for 2020 babies.

Could the drastic decrease in cognition simply be given the novelty of having a new face that is wearing a mask? There are several anecdotal experiences in which an infant is unable to recognize their own father after they shave their beard or hair.

Given the development of facial recognition even in the absence of a fear response a child exposed to a masked face is only getting about 50% of the information they would normally get from an unmasked individual. Kids don't develop full holistic facial recognition until the age of 6 if I am not mistaken.

I think it would be difficult to ace an exam in which you are only presented 50% of the instructions, but I am unfamiliar with the testing used. How much is guided by facial expressions that require more than just the top half of the face?

On 2021-09-14 21:49:42, user Cengiz Kiliç wrote:

Dear Dr Swedo et al,

We read with enthusiasm your consensus paper. We are looking forward to its publication, since it is very timely and much needed. We believe such a consensus, reached at by an international panel of experts, and using rigorous criteria, will be very helpful to set the main principles for advancing research, in an area where little is known. Such a clinical guideline will limit the circulation of several existing diagnostic criteria sets that have little relevance with the clinical presentation of the disorder. We especially appreciate your (strongly) emphasizing the fact that misophonia is a sound-sensitivity disorder, and not a disturbance of any sensory input.

At our Stress Assessment and Research Center (STAR) of Hacettepe University, Ankara, we have been conducting research on misophonia (as well as other stress disorders) since 2015. Our first study*, which was just published last month, presented prevalence rates on a random population sample, using our own proposed diagnostic criteria (it is a pity that our study did not appear in time to be included in your literature search). Our second study was a treatment study comparing the effects of psychoeducation, filtered music and exposure in 60 misophonic outpatients, which we are preparing for publication. Our follow-up study (of the population-study sample) is still ongoing. We touched upon the limitations of the existing proposed diagnostic criteria sets in our BJPsych paper’s supplement, and would be happy to share our views in more detail (if requested).

Sincerely,

Cengiz Kiliç, Professor of psychiatry<br /> Gökhan Öz, psychiatrist <br /> Burcu Avanoglu, psychiatrist<br /> Songül Aksoy, Professor of audiology

Misophonia Research Group, Stress Assessment and Research Centre (STAR)<br /> Hacettepe University, Ankara

Email: star@hacettepe.edu.tr<br /> Phone: +90-312-3051874

* Kiliç C, Öz G, Avanoglu KB, Aksoy S. The prevalence and characteristics of misophonia in Ankara, Turkey: population-based study. BJPsych Open. 2021 Aug 6;7(5):e144. doi: 10.1192/bjo.2021.978. PMID: 34353403; PMCID: PMC8358974

On 2023-06-29 09:40:33, user Nensi wrote:

The idea behind this study is truly interesting and highlights the critical importance of addressing the issues surrounding poor reporting and the quality of systematic reviews.<br /> However, some things could be changed to improve the quality of this study. Below you can find some of my comments regarding your manuscript.<br /> 1) The manuscript could use extensive language editing, as there are many grammatical and spelling errors. Many language editing programmes can be very useful for these purposes (Grammarly, Instatext etc.).<br /> 2) You begin the Methods section with the aim of your study, but you state that the aim was to do a study. You can see why that does not make sense. The aim of your study was to do a study. You should report here the specific purpose or what you wanted to assess (for example, the aim was to assess the reporting quality of systematic reviews published by authors from India from 2015 to 2020).<br /> 3) In Results, you decided to report the data in text and with two figures. However, when you have so much descriptive data, it could be presented more clearly with just a table. The table allows the authors to store large amounts of data in a small place, making it easier for the readers to go through the data and understand the results. <br /> 4) Another detail about presenting the results is that they should be written in the past tense instead of the present tense you used.<br /> 5) Also, when presenting descriptive data, it is recommended to report both absolute and relative numbers (for example, „Only 20 (15%) of the reviews have been registered in PROSPERO registry“).<br /> 6) You could benefit from using STROBE reporting guidelines for observational studies (https://www.equator-network... "https://www.equator-network.org/reporting-guidelines/strobe/)"). Reporting guidelines are handy in ensuring you have reported everything that needs to be written in an article.<br /> 7) There is also much room for improvement regarding the referencing. A small detail would be the in-text referencing where you put [1] after the full stop. So the general rule would be that if you use brackets, it should be placed inside the sentence, and if you want to put the number in superscript, it should be after the sentence. That could use a bit of tidying up. <br /> 8) Additionally, regarding the referencing, you have used different styles of referencing in the reference list and some of the references are not referenced correctly or at all. There are many programmes that can help you organize and write the references (EndNote, Zotero, Mendeley etc.).<br /> 9) And one more thing for future referencing, even though a study is methodological, it should be preregistered. All studies should be preregistered to promote open science and transparency in conducting scientific research.<br /> I hope these suggestions will help. Good luck with your work!

On 2020-12-20 18:23:25, user Martin Reijns wrote:

None of the reported mutations in the new SARS-CoV-2 variant (lineage B.1.1.7; VUI-202012/01) that is becoming more widespread in the UK impact on the E gene, N1 or N2 assays. Our N1E-RP and N2E-RP multiplex assays will therefore still detect this new strain.

https://virological.org/t/p...

The M gene assay that we refer to in our manuscript is also not affected by the reported changes. However, the S gene assay that we refer to would likely no longer effectively detect this new strain because of a 6 nt deletion within the probe binding site.

On 2021-12-16 21:16:38, user tshann wrote:

A little confused at this statement from the article:

While variants and waning efficacy are relevant, SARS-CoV-2 vaccines reduce the risk of infection, transmission, and severe illness/hospitalization in adults

Someone'll likely correct me here, but to my dim memory, Walensky, CDC and Faucci himself have admitted the vax's don't stop transmission or prevent infection. Am I wrong?

Peace

On 2021-09-15 11:40:15, user japhetk wrote:

Although this study is about analyzing time series data, the research method is inappropriate because it uses ordinary multiple regression analysis without analysis for time series analysis. Here is a page that explains the basics of analysis for time series data.<br /> https://logics-of-blue.com/...

Based on this preprint that spread on social media, people have the misconception that delta variants have nothing to do with the spread of infection and that vaccines spread infection. I think the authors should refer to it and revise the manuscript as soon as possible.

Also, in the data I have, from April to the end of August, the share of daily delta variants, the number of days elapsed, and the raw data of vaccination rates each show a correlation of 0.95 or higher. These highly correlated variables can cause multicollinearity, which can lead to strange results. Simply put, these variables cannot be included in the same model.<br /> I also prepared my own data for Tokyo from April to the end of August, but when I used the same simple multiple regression analysis as the authors did, including human flow, the number of days elapsed, and these variables (which is an inappropriate method of analysis for a number of reasons, as explained above), the vaccination rate of tokyo (+ 14 days) was negatively correlated with rt (- 14 days) and the delta variants share was positively correlated with rt, and the authors' results could not be replicated.

I referred to the apple mobility data (transit and walking) for the population flow.<br /> The following page for RT (-14 days) of Tokyo.https://uub.jp/cvd/cvd.cgi?T=5&Y=21...<br /> Delta variant share for owid data. (-21 days, Blank days were complemented by weighted averages.)

On 2020-12-26 19:39:53, user Sam Smith wrote:

TreatEarly / promising drugs.<br /> https://www.treatearly.org/...<br /> A large multi-center observational study with hospital inpatients in France showed that SSRIs in general were protective against covid. The drug with the greatest sigma-1 activation in the study (Fluoxetine in that case) had the greatest protection. The hypothesis of the researchers at Washington University is that the protection comes from the activation of Sigma-1. S1R is known to inhibit a cytokine, a chemical in our body that gets activated in certain infections, such as Covid-19.

On 2020-07-27 19:36:43, user Andrew Bowdle wrote:

Long et al reported SARS-CoV-2 RT-PCR testing of 20,912 patients[1]. There were 19,035 (91%) patients who tested negative. Of these negative patients, 626 were retested within 7 days, and 22 (3.5%) were positive. While not claiming to have measured sensitivity, the authors stated that “false negative results at the time of initial presentation do occur, but potentially at a lower frequency than is currently believed”. Some have interpreted this study as showing that the sensitivity of the SARS-CoV-2 RT PCR assay is high (>95%). This is an incorrect interpretation of the data shown in Long et al. High sensitivity means that, among people who actually do have SARS-CoV-2 only a small fraction will have a test result that is falsely negative. On the other hand, the 3.5% that Long et al report is an attempt to estimate something quite different, namely among all people with a negative test result, the fraction that actually does have SARS-CoV-2. This fraction being only 3.5% means that the vast majority of negative test results are true negatives, reflecting the fact that the prevalence of the virus is low in the population being tested. Therefore, a rate of 3.5% does not imply good sensitivity but rather low prevalence. In general, false negatives as a percent of negative results has to be less than the prevalence of the condition in the population being tested.

Consider a simple hypothetical example. Assume that the prevalence of SARS-CoV-2 in the population being tested is 10%, RT-PCR specificity is 100% and sensitivity is 50%. Then out of 10,000 people tested there will be 9,000 true negative results and 500 false negative results (half of the 1,000 people who truly have SARS-CoV-2). Thus, 500/9,500 = 5.3% of the negative test results are false negatives.

Upon retest, 250 of the 9,500 (2.6%) of the original negative test results will be positive, assuming the sensitivity is still 50% in the 500 people with SARS-CoV-2 who falsely tested negative the first time (which may not be true). The 2.6% corresponds to the 3.5% reported by Long et al. Thus, in this example, sensitivity is poor, yet the observed false negatives are only 2.6% of all negative results.

A number of reports have suggested a moderate sensitivity for SARS-CoV-2 RT-PCR of around 70% (30% false negative)[2]. Calculations similar to those in the example above show that if prevalence is 15%, specificity is 100% and sensitivity is 70% then the expected results are almost the same as those found by Long et al. Different combinations of prevalence, sensitivity and specificity also give results similar to Long et al. It is incorrect to interpret Long et al as showing that the SARS-CoV-2 RT-PCR test has good sensitivity.

References

1. Long DR, Gombar S, Hogan CA, et al. Occurrence and Timing of Subsequent SARS-CoV-2 RT-PCR Positivity Among Initially Negative Patients. Clin Infect Dis 2020;10.1093/cid/ciaa722.

2. Woloshin S, Patel N, Kesselheim AS. False negative tests for SARS-CoV-2 infection - challenges and implications. N Engl J Med 2020;10.1056/NEJMp2015897.

Posted by Kevin Cain PhD, Srdjan Jelacic MD FASE, Kei Togashi MD MPH, Andrew Bowdle MD PhD FASE

On 2020-08-01 03:03:30, user Peter Lange wrote:

Thanks this is a really important paper. I wpuld like to see it in a high inpact journal. If I could make the following suggestions to enhance:<br /> - using STROBE checklist will improve the reporting and ensure no required points are missed. Many journals will require compliance with this for publication.<br /> - the abstract would be more compelling with the number of participants<br /> - the selection of participants could be better described - were these all the participants available in that period? Were 150 participants selected from the initial date?<br /> - though a retrospective observational study of routinely collected data nevertheless some journals will require a statement from the local ethics board - that full application was not required - to be obtained<br /> - the use of CFS in the regression analysis as an ordinal point scale gives a result just barely significant. The result may be strengthened by uniting categories 1-3 4-6 7-9 which is reasonable given numbers. Alternativelya dichotomous division at CFS 5. Just be careful to state this was post-hoc analysis. If not doing that stating the rsult more strongly "OR 1.25 (1.00-1.50) for mortality per point on the 9 point CFS" emphasises the importance and validity of the result.<br /> - where using medians to describe samples interquartile range can add additional information as to the distribution of the observations.

• i think there will be some interest internationally about the absence of mechanical ventilation in any participant. The use of respiratory support It would be informative to discuss why before the final section.

• the tables are pretty dense and hard to read. Some spacing would help.

All the best I hope to see this in print soon and consider an international follow-up

Peter Lange

On 2021-01-07 21:56:18, user Joseph Guinness wrote:

Hello, thanks for conducting this interesting study. We conducted a similar study last year and found similar results:<br /> https://researchers.one/art...

One potential issue with your design is that by taking the top 50 finishers at each race, you may be preferentially selecting people who respond more to Vaporflys: the so-called "super-responders". Put simply, if someone is a super responder, they are more likely to finish in the top 50 when they switch to vaporflys. This is somewhat ameliorated by the fact that a runner would have to finish in the top 50 in a race without the Vaporflys, but not completely.

For example, suppose two runners finish 49th and 50th in Boston without the Vaporflys, then they both switch to Vaporflys for Chicago, but one of them is a super responder and the other isn't. Then the super-responder is more likely to finish in the top 50 in Chicago, while the non-super-responder is not. If that happens, the super-responder gets kept in the study, while the non-super-responder gets dropped. Of course, it doesn't have to work out way, but the odds are tilted towards keeping the super-responder and dropping the non-super-responder.

We addressed this issue in our study by sampling runners according to a performance standard before the Vaporflys entered the market.

I'm guessing that if you addressed this issue, the results wouldn't change a lot, but it's something to consider.

It was a bit difficult to follow your description of how the analysis was done, specifically how you controlled for marathon difficulty and conditions of a specific race in a specific year. It might be helpful to write down a statistical model or go through the calculation for a few runners.

Overall, this is really interesting. We can appreciate (from experience) how tedious it is to comb through hundreds of race photos and identify the shoes runners wore.

On 2021-08-18 19:05:43, user FABIO LIPIANI wrote:

Studies addressing immunosenescence in the immune system have expanded to focus on the innate as well as the adaptive responses. In particular, aging results in alterations in the function of Toll-like receptors (TLRs), the first described pattern recognition receptor family of the innate immune system. Recent studies have begun to elucidate the consequences of aging on TLR function in human cohorts and add to existing findings performed in animal models. In general, these studies show that human TLR function is impaired in the context of aging, and in addition there is evidence for inappropriate persistence of TLR activation in specific systems. These findings are consistent with an overarching theme of age-associated dysregulation of TLR signaling that likely contributes to the increased morbidity and mortality from infectious diseases found in geriatric patients.

On 2020-08-04 14:44:36, user Tammy Spain wrote:

This is such an important study. I applaud the authors for bringing good evidence to the discussion about the role of children in transmission of SARS-CoV2. So much of the dogma around this question has been centered on anecdotal information.

On 2020-07-05 00:22:50, user Philip De Groot wrote:

1.5 gray is the equivalent of 1,500 mSv. 100 mSv is the top of the low dose bracket. Are the authors claiming that an exposure of 1,500 mSv is safe, that it constitutes a low dose?

On 2020-08-08 22:41:29, user Erhannis Kirran wrote:

Spelling error, Line 55, "Covit-19"

On 2021-01-19 19:01:38, user Filip Hrivnák wrote:

That voluntary. In general, we are losing the last signs of the rule of law

On 2021-10-05 11:12:38, user Jonna Zizak wrote:

What were the rates of the unvaccinated during the same time period?

On 2020-08-29 10:12:31, user Rebecca Weisser wrote:

@MinSeoKim_MD Your paper of May 18 showed benefit of HCQ +antibiotic to patients with moderate Covid compared to Lopinavir–Ritonavir and standard care. Your paper of July 7 hid that benefit by adding in 173 patients with mild Covid who all recovered without treatment. Why did you do that?

On 2021-06-30 13:51:55, user Adam Mercy wrote:

It is reassuring to some, but borderline insanity to others that we have to prove we have an immune system. We knew early in 2020, that prior T cell immunity was present in probably 50%+ of the population, from prior coronaviruses from as far back as 15y (or longer).

Covid likely is a patient-specific immune hypersensitivity. Some say MCAS, it may turn out to be. If that is the case, vaccines or not, those patients need drugs -- which implies drug therapies are the only way out.

And yet, the conclusion to this piece is about prioritizing vaccines. Scientists take a look at data from nation states like Mexico. Not small trials, massive interventions at scale. Or India. You are making a blunder which will meme''d about till the end of time. See our twitter on how to save your reputations.

On 2022-01-20 12:16:06, user Daniele Sardinha wrote:

10.4236/aid.2021.114039 foi publicado

On 2021-03-03 17:21:39, user Maxim Sheinin wrote:

It seems that an important limitation of the study is to treat Covid-deceased individuals as representative of the average within the population (as reflected by the use of actuarial tables), while we know that people with comorbidities (who likely face shorter life expectancy) are also more likely to die of Covid. While this analysis may be too complex, there's another easier and impactful one: nursing homes. As of early Dec 2020 ~39% of Covid deaths occurred in nursing homes (https://www.nbcnews.com/kno... "https://www.nbcnews.com/know-your-value/feature/39-covid-19-deaths-have-occurred-nursing-homes-many-could-ncna1250374)"). Nursing home residents face reduced life expectancy. For example this paper (https://www.ncbi.nlm.nih.go... "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143238/)") found ~2.2 years median life expectancy post-admission for nursing home residents with an average age of ~85, while the authors' analysis would have assumed at least ~4.5 years (Appendix table 1). Thus current analysis is likely to overestimate true YLLs

On 2021-10-18 15:21:44, user Dr Gareth Davies (Gruff) wrote:

An interesting study. Is the raw data available? It would be very illuminating to see a plot of individual *uncategorised* 25(OH)D status against seropositivity, along with standard errors plotted for each data point to be sure that the apparent U-shape is real and not e.g. an artefact of categorisation of continuous data with known, large standard measurement errors.

The number of individuals per category is relatively small, and the standard errors on vitamin D assays relatively very large (and potentially heteroscedastic), and this, combined with the natural variance in the study population, uneven bin sizes, and the presence of multiple confounding variables introduces potentially very large biases and uncertainties.<br /> Fischer's Exact Test is not contructed to be able to take into account factors such as these, and thus the stated p values are not really meaningful, and potentially misleading.<br /> Plotting fit curves along with reduced y-axis range gives a false impression of a precise trend which seems unjustified by these data.

For example, the abstract states that "This trend repeated when split into subgroups of age, sex, ethnicity, BMI, and co-morbidity status", but this *not* in fact true for the "age < 50" and "zero comorbidities" groups where the U-shape trend is not present.

I would urge caution interpreting any apparent trend and also the meaning of 'seroconversion'. There seems to be an implicit assumption that "detected seroconversion" is equivalent to risk of harm from disease. If the trend turns out to be an artefact of the analysis, any interpretation is premature. If the trend turns out to be real, there still may be zero implications for risk of harm. High vitamin D serum concentrations could, for example, lead to stronger host immune response and antibodies, which could account for the results.<br /> It would be useful to include - if possible - some measure of actual disease severity (if any) in the individuals who tested positive.

I hope this is helpful feedback for a future draft of this preprint.

Best wishes

Gareth

On 2020-09-24 06:47:06, user Subhajit Biswas wrote:

Pleased to see that other scientists are supporting with further evidences, the trend we had observed and reported as early as April 2020.

Based on non-overlap of dengue and COVID-19 global severity maps and evidences of SARS-CoV-2 serological cross-reactions with dengue, we proposed that immunization of susceptible populations in dengue non-endemic regions with available live-attenuated dengue vaccines may cue the anti-viral immune response to thwart COVID-19.

https://www.preprints.org/m...

Thanks to Dr Nicolelis and team from Brazil to provide further evidence to our original proposition that COVID-19 is less severe in highly dengue-endemic regions.

The chronology of this dengue covid conundrum, as it stands now, has been meticulously reported by The Print (https://www.msn.com/en-in/h... "https://www.msn.com/en-in/health/medical/dengue-antibodies-could-provide-immunity-against-covid-brazil-study-suggests/ar-BB19k0OB?li=AAggbRN)").

Amazing! Nature has its own ways of controlling parasite aggression! Antigenic correlation between a flavivirus and a coronavirus was unprecedented.

*Dengue vaccines could be tested in SARS-CoV-2 animal models and tried in dengue non-endemic countries*.

*Use in dengue-endemic countries may be problematic as such vaccination can elicit antibody-dependent enhancement of subsequent dengue infections*.

Our publications in this area to support our proposition: <br /> (1) COVID-19 Virus Infection and Transmission are Observably Less in Highly Dengue-Endemic Countries: Is Pre-Exposure to Dengue Virus Protective Against COVID-19 Severity and Mortality? Will the Reverse Scenario Be True? Clinical and Experimental Investigations, Volume 1(2): 2-5. <br /> (https://www.sciencereposito... "https://www.sciencerepository.org/covid-19-virus-infection-and-transmission-are-observably-less-in-highly_CEI-2020-2-105)")

2. Nath, H., Mallick, A., Roy, S., Sukla, S., & Biswas, S. (2020, June 19). Computational modelling predicts that Dengue virus antibodies can bind to SARS-CoV-2 receptor binding sites: Is pre-exposure to dengue virus protective against COVID-19 severity?. <br /> https://osf.io/dutx4/

3. Dengue antibodies can cross-react with SARS-CoV-2 and vice versa-Antibody detection kits can give false-positive results for both viruses in regions where both COVID-19 and Dengue co-exist<br /> https://www.medrxiv.org/con...

On 2021-07-27 14:06:37, user VailShredBetty wrote:

The conclusion of less diversity in the vaccinated leading to less infection? How do we draw this conclusion based upon less diversity? I think it takes time for a virus to work around a vaccine, no? Seems a little presumptuous. Logically speaking, this type of virus, like flu, will not be 'eradicated' by a vaccine....like all the others. (smallpox and polio were not eradicated by a vaccine....those are literally the only two examples people often give) Life will find a way and when we let viruses run their course, proper herd immunity is reached. lessons fro the past (compulsory smallpox vaccination) created more issues and actually spread the infection with those vaccinated 3 and 4 times dying at higher rates. Seems like this study was stopped way too early to make the conclusions given.

On 2021-10-27 22:37:44, user yury g wrote:

(1) Would you consider showing separately the hazard ratios in the Appendix by time-between vaccination and infection - e.g. for (a) less than three months post vaccine, and for (b) greater than three months post vaccine? This might contain a useful signal for the public health discussion around risks of waning immunity against infection in general population....... (2) Would you consider showing separately the hazard ratios in the Appendix for (a) infections taking place before the delta variant took hold, and (b) infections taking place after the delta variant took hold? Many thanks