Good point raised .Covid-19 latent period currently not known . But assume according to admitted hospital patients 10-14 days. But, virus further replicate and reappearance chance again.

Anti body develop after attack as per hospital patient information expected to be 4-6 months and some patients 9 month

It should be quite sure that since there are resisual symptoms and that in some cases postivity to tests continue eìweeks after, similarly to human polio vrus and HIV as well, also SARS-CoV-2 has preferential tissues/organs where remains latent at immunoprivileged sites until most favourable conditions allow to reactivate or replicate again. No doubts about this, but where ? ... and by which mechanisms ?

Agree with Veronesi paolo Alberto. It attack various organ in body. Valuable information you want in this article.

SARS COVID 19A MEDICINAL CHEMISTRY APPROACH

https://doi.org/10.2174/1389557521666210126125633

Dear Annwyne,

see my article where I discuss the possibility of latency/senescence for SARS Cov-2/variants

Procunier William. The Perfect Storm and A Global Call to Reason: An Evolutionary Perspective on The Existential Threat of Covid-19 to Humanity. Clin Rev Cases. 2020; 2(1): 1-4

• Issue 1 | 1 of 4 Clin Rev Cases
• https://www.researchgate.net/profile/William_Procunier

maybe

https://www.nature.com/articles/d41586-020-02598-6 - A wide ranging symptoms of Covid19 .

While a possibility of virus lurking in immunoprivileged sites in the body causing long COVID-19 does exist, one can probably explain lasting symptoms with autoimmunity alone. There is a growing literature pointing at autoantibodies targeting a long list of host proteins causing multiple autoimmune complications in patients. Any one of those might be responsible for significant portion of symptoms associated with the post-acute stage of the disease in some of the patients. Examples are mentioned in recent publications:

Article The SARS-CoV-2 as an instrumental trigger of autoimmunity

Preprint Diverse Functional Autoantibodies in Patients with COVID-19

could be a combination of explanations given to account for apparent Sars Cov-2 latency/senescence (long covid)

"...

From another point of view, various coronaviruses have been identified by serological techniques in a wide variety of neurological pathologies, such as Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and optic neuritis [7,19,31,32]. Viral persistence of Nidovirus (coronavirus) in CNS has been described by Lavi et al. in 1999 [33]. Coronaviruses 229E, 293, and OC43 have been isolated from the cerebrospinal fluid and the brain of patients with multiple sclerosis [31]. The immune response after infection could participate in the induction or exacerbation of multiple sclerosis outbreaks in susceptible individuals [5]. This would also support the idea that apparent reinfections of COVID-19 patients who passed the disease, return to suffer it with or without neurological symptoms, due to the persistence of the virus in neural tissue. This has been described in varicella-zoster virus infection [34,35]. In COVID-19, findings from a small group of cases suggested that there was currently evidence for reactivation of SARS-CoV-2, has no specific clinical characteristics to distinguish from primoinfection [36].

In addition, other viruses, such as the herpesviruses including the herpes simplex virus and the herpes zoster virus, among others, reach from the nerve endings to the spinal ganglia and remain in a state of latency with low replication, until a reactivation due to a disturbance of the immune system [37]. Nipah virus (a paramyxovirus) causes many of the same respiratory and neurological symptoms that SARS-CoV-2. Kevin R in 2020 [38] showed a reactivation, months or years later of the Nipah virus from latent infections. Both viruses, (SARS-CoV-2 and Nipah virus) selectively infect neurons, and this enables them to evade attacks from the immune system of the host. This occurs because, as is known, almost all T‐cell (lymphocytes) activations require that an antigen be presented by another cell, such as a dendritic cell, on a specific surface protein known as a major histocompatibility complex (MHC) or human‐leukocyte-associated (HLA) protein in humans [39]. Lymphocytes with the MHC requirement for antigen presentation are activated. MHC class II for presentation to cluster of differentiation (CD)4 T cells and MHC class I for presentation to cytotoxic CD8 T cells [39]. But neurons carry very few of these MHC proteins, so they cannot easily present viruses on MHC class I to cytotoxic CD8 T cells to induce an attack on the infected neurons [37]. "

Altable Pérez M, De la Serna JM. Neuroinvasion and Viral Reservoir in COVID-19. Cureus. 2020;12(10):e11014. Published 2020 Oct 18. doi:10.7759/cureus.11014

Article Neuroinvasion and Viral Reservoir in COVID-19

Thank you for sharing this Marcos, fascinating contribution.

I'm wondering if this question has been studied in the field of myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS) or ME/CFS.

Very interesting and more reason for in depth research on understanding the pathology and epidemiology of long covid-19 especially given the rising incidence in functional variants and reverse zoonotic events globally

Regarding LongCovid, apart from ev. virus persistence what about the possible link to dysautomia and/or MCAS? (See e.g. "Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome" Lawrence B.Afrin Leonard B.Weinstock Gerhard J.Molderings https://doi.org/10.1016/j.ijid.2020.09.016 )

Covid19 suffered patients after recovery remain weak immunity. Major damage occured in lungs due to virus attack that in words remain latent in patients. Lungs by providing oxygen to body maintain immunity. After covid lungs some patients not fully recovered and this as latency of covid19 remain as consider but actually not. It's due to lung impairment.

Yes, Gautum it cannot be denied that serious lung damage and hypoxia are significant factors in the effects of COVID 19.

However, according to a recent publication in ‘The Lancet’, a wide array of neurological manifestations have been reported in several COVID 19 case reports, such as encephalopathy, Guillain-Barre syndrome and SARSCoV-2 has been detected in CSF. The commonly recognised COVID 19 symptoms of ageusia and anosmia are sometimes the only symptoms and associated with the virus. SARSCoV-2 may enter the CNS by infecting the olfactory receptor neurons when reaching the olfactory bulb by passing through the neuroepithelium of the olfactory mucosa. This accesses the mitral cells and the olfactory nerve, enabling the virus to spread to the hippocampus.

Some acute cerebrovascular disease is emerging, including stroke and other vascular events, some involving hypercoagulable states with elevated C-reactive protein.

Several other coronaviruses are neuroinvasive and neurotropic, however SARCoV-2 has not been detected in the CNF of a majority of the COVID 19 patients tested. Having stated that, some individuals may have COVID-19-related encephalitis resulting from immune- mediated inflammatory mechanisms, in the absence of direct virus invasion.

Alessandro Pezzini and Alessandro Padovani, Lifting the mask on neurological manifestations of COVID-19, Nature reviews, Neurology, 2020, 16:836.

Mark A Ellul, Laura Benjamin, Bhagteshwar Singh, Suzannah Lant, Benedict Daniel Michael, Ava Easton, Rachel Kneen, Sylviane Defres,

Jim Sejvar, Tom Solomon, Neurological associations of COVID-19, Lancet Neurology 2020; 19: 767–83

Anneyne as per manifestation covid no latency. While it enter in body NSP 1-16 replicate and attack all organs and alter function untill body adapt and people consider HERD immunity.

In this article.

SARS COVID 19 A MEDICINAL CHEMISTRY APPROACH

10.2174/1389557521666210126125633

I feel all of us focus on latency and did research nobody look after affect of covid to population and to protect people sufferd from covid. Also analysed to further research on patent suffered from covid

Congratulation for exellente work

Excellent learning.

Long covid may be pulmonary, neurological , cardiovascular or musculoskeletal mostly

Any hematological evidence of long covid?

In answer to some haematology questions, with regard to lymphocytes and haematological conditions.

Meta-analysis and systematic reviews of studies that investigated the lymphocyte count, on admission to intensive care units, showed that lymphopenia was significantly associated with poor patient outcomes in COVID-19 patients. This could be used as a marker, especially in younger patients, as an indication of severity of disease. Lymphopenia was defined as less that 1100/μ L associated with a threefold risk of poor outcome.

One hypothesis to explain this phenomenon is that lymphocytes express ACE2 and that they themselves may be the targets for SARSCoV-2, and that an increase in proinflammatory cytokines, such as, IL-6, in COVID-19 may reduce lymphocytes further. This level of T cell exhaustion and reduced functional diversity in peripheral blood may be an indication of severe progression in COVID-19 patients.

Thus, lymphopenia occurs in COVID-19 patients with prolonged unresolved viral infection. Also, lymphocytes within the oral mucosa express the ACE2 viral receptor for COVID-19 and it has been suggested that this may be a possible cause of the lymphopenia observed in severely affected COVID-19 patients, where there may be virus-induced apoptosis of T cells.

Haemoglobinopathy, hypoxia and cell iron overload might have a possible additional roles in COVID 19 patients and oxygen-deprived blood disease, with iron metabolism dysregulation, haemoglobin denaturation should be taken in consideration.

· Huang C, Wang Y, Li X, Ren L, Zhao J, et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497-506.

· Huang I, Pranata R (2020) Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis. J Intensive Care 8:36.

· Liu J, Liu Y, Xiang P, Pu L, Xiong H, et al. (2020) Neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage. medRxiv.

· Lin L, Lu L, Cao W, Li T (2020) Hypothesis for potential pathogenesis of SARS-CoV-2 infection--a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect 9: 727-737.

Zheng HY, Zhang M, Yang CX, Xhang N, Wang XC, et al. (2020) Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol 17: 541-543.

Cavezzi A, Troiani E, Corrao S. COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review. Clin Pract. 2020 May 28;10(2):1271. doi: 10.4081/cp.2020.1271. PMID: 32509258; PMCID: PMC7267810.

useful additional and potentially practical insights

WSP

I realise that thrombophilia should also be mentioned, as SARS-CoV-2 induces the cytokine storm that activates IL-6 that damages the microvascular system, thus activating the coagulation system. This COVID 19 effect also inhibits fibrinolysis and anticoagulation process that induces thrombopoietin synthesis in the liver leading to thrombosis in microvessels. COVID-19 patients with high levels of D-dimers and conditions causing hypercoagulation are particularly susceptible to this process. It is recognised that extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation.

Some common types of thrombophilia, in the general population, create an imbalance in haemostatic and fibrinolytic pathways affecting the proteolytic clotting cascade thus leading to thrombosis and the presence of any of these conditions could exacerbate the COVID 19 induced thrombophilia.

Thakur V, Ratho RK, Kumar P, et al. Multi-Organ Involvement in COVID-19: Beyond Pulmonary Manifestations. J Clin Med. 2021;10(3):446. Published 2021 Jan 24. doi:10.3390/jcm10030446

@Voskoboinick Andrey

You have copied/pasted your answer from the following link shared by Jaydip Datta in this thread.

https://www.nature.com/articles/d41586-020-02598-6

Please add the original source to your answer to avoid plagiarism.

Thanks!

Arvind, thank you so much for your vigilance supporting this discussion and contribution

Acute COVID-19 usually lasts until 4 weeks from the onset of symptoms, beyond which replication-competent SARS-CoV-2 has not been isolated. Post-acute COVID-19 is defined as persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms.

[01/04, 07:52] Dr

A post-acute outpatient service established in Italy (hereby referred to as the post-acute COVID-19 Italian study)3 reported persistence of symptoms in 87.4% of 143 patients discharged from hospital who recovered from acute COVID-19 at a mean follow-up of 60 d from the onset of the first symptom. Fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%) and chest pain (21.7%) were the most commonly reported symptoms, with 55% of patients continuing to experience three or more symptoms.

seen CKD and malignancy patients having persistent covid PCR positive. Have some with reappearance also with fever and symptoms after 2 to 3 months. Difficult to define them as persistent/reinfection

Thanks Pranav, that's really interesting, what do you think is going on immunologically?

maybe

Dear Pranav Ish

Contrary to your unpublished observation, in the study below, there was no difference in asymptomatic COVID-19 cases in cancer patients and health care workers.

Article The Potential Role of Immune Alteration in the Cancer–COVID1...

Further to the topic of immune-privileged sites to SARS-CoV-2 in human body, Eye has attracted contested debate as in the editorial below: However, it it not part of the symptoms in people with long-COVID.

Is Eye Immune-Privileged to COVID-19 Infection?

https://link.springer.com/article/10.1007/s42399-020-00723-0#:~:text=As%20such%2C%20the%20eye%20does,more%20evidence%20than%20currently%20available.

I may have a biased sample frame, sir. Will try to look more carefully. The issue we face with hemat malignancy and CKD patients is that for months their PCR is positive and they have to undergo therapy/dialysis in separate isolation.

mechanisms may be a poor immune response, high viral load, or simply persistence of non-infective loads ( as CT values do increase). Unfortunately, we are unable to culture or do any genetic analysis.

Reasons for Persistence of SARS-CoV-2 Positivity on RT-PCR

These may include (1-2):

1. Persistence of inactive SARS-CoV-2 RNA (viral garbage), that certain people may continue to have for a long period despite being asymptomatic, but giving a false positive viral RNA-based PCR. The viral cultures in there people were negative and these people did not transmit the COVID-19 to others.

2. True false positives possibly due to cross-reaction to other coronaviruses.

Therefore, CDC and WHO has done away with repeat COVID-19 PCR testing before discontinuing isolation or deciding discharge of hospitalized patients, and criteria is based on the improvement in symptoms from the index day of first diagnosis.

Before that even we have been perplexed (3 on researchgate) due to repeated positive and negative PCR based tests in asymptomatic COVID-19 patients leading to unnecessary prolonged hospital stay, anxiety for patients, and wastage of resources.

Only way to confirm a persistently positive SARS-CoV-2 test as re-infection is viral cultures and when variants are suspected by genomic studies (these are not routinely done because of expense and lack of availability everywhere) and are not recommended in asymptomatic patient unless the contacts of such patient get symptoms suggestive of COVID-19.

1. Article Persistent SARS-CoV-2 RNA Shedding without Evidence of Infec...

2. Preprint False positives in reverse transcription PCR testing for SARS-CoV-2

3. https://www.researchgate.net/post/What_are_the_interpretations_and_implications_of_having_negative_followed_by_positive_RT-PCR_tests_in_COVID-19_patients

So informative, Muhammad,

Thank you

It is absolutely true that investigation into the possibility of latent COVID 19 infection is an important issue in this current pandemic.

That is why I will read the answers and opinions on this topic with great interest.

see the latest publication in Genetic Engineering and Biotechnology confirming a type of latency/senescence for Sars-Cov-2 as was suggested earlier from Procunier William. The Perfect Storm and A Global Call to Reason: An Evolutionary Perspective on The Existential Threat of Covid-19 to Humanity. Clin Rev Cases. 2020; 2(1): 1-4. and others

Eminent MIT Scientists Defend Controversial SARS-CoV-2 Genome Integration Results

https://www.genengnews.com/insights/eminent-mit-scientists-defend-controversial-sars-cov-2-genome-integration-results/?utm_medium=newsletter&utm_source=GEN+Daily+News+Highlights&utm_content=01&utm_campaign=GEN+Daily+News+Highlights_20210513&oly_enc_id=9774C4169245E0T

The reasons mentioned for persistent positive , well summarised

Thank you sir

Article Neuroinvasion and Viral Reservoir in COVID-19

sir, I ask what is the role/influence on therapeutics if we isolate the virus from these affected sites or not late in the illness. Do we consider giving antivirals in such patients as most symptoms late in illness are inflammatory requiring steroids etc

Exceptional prolonged SARS-CoV-2 infection for 216 days in a treatment resistant- chronic HIV infected patient with Coronavirus mutations for 30 times.

Patients with long-COVID are having usually no evidence of infection. However, immunocompromised patients may harbor the SARS-CoV-2 for prolonged periods.

Previously it has been reported from South Africa that HIV infection alters SARS-CoV-2 responsive immune parameters, however not changing the clinical outcomes in COVID-19 disease (1).

Now a report of South African woman with antiretroviral treatment resistant HIV is reported having the evidence of prolonged SARS-CoV-2 infection for 216 days. The virus mutated at least 30 times inside her during course of her illness (2).

This report indicates that in exception immunocompromised patients prolonged persistence of SARS-CoV-2 infection can lead to multiple mutations.

1. Preprint HIV infection alters SARS-CoV-2 responsive immune parameters...

2. Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV

https://www.medrxiv.org/content/10.1101/2021.06.03.21258228v1.full.pdf

Long COVID is currently considered to be the prolonged effects of SARS-CoV-2 that persist after clearance of the live virus. Patients may remain COVID-19 PCR positive but this reflects persistent shedding of inactive virus.

However, we still have much to learn about this complex virus. So it is not impossible that some of what is considered long-COVID-19 is actually persistent infection. Furthermore, a few patients (with and without long-COVID may have reservoirs of latent virus.

One reason for the persistence of positive PCR tests for SARSCoV-2, without evidence of viral replication may be the integration of viral sequences into host DNA.

It has been observed that DNA copies of SARS-CoV-2 sequences can be integrated into the genome of infected human cells. SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the DNA of human cells in vitro and it is thought that the transcription of the integrated sequences might be responsible for some positive PCR tests seen in patients.

SARS-CoV-2 viral RNA continues to be detected in the absence of virus reproduction, in some cases. DNA copies of viral sub-genomic RNAs may integrate into the DNA of the host cell by a reverse transcription mechanism. Baring in mind that SARSCoV-2 is a positive single strand RNA virus, the existence and detection of negative strand viral RNA sequences, present up to 40-50% of total viral RNA sequences, indicates that there are retro transposon-medicated integration events, where genetic elements can jump to different locations within a genome. This is information is documented in the attached paper by Zhang.

See for example recent https://directorsblog.nih.gov/2021/06/08/how-covid-19-can-lead-to-diabetes/

Persistence of SARS-CoV-2 RNA in lung tissue after mild COVID-19.

However, this was not an active virus (1)

1. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00240-X/fulltext

What's the link between COVID-19 and black fungus?

An association has been made between the ubiquitous black mould, mucormycosis (black fungus) and the steroid therapy used to treat COVID 19 in India. Also with COVID-19 patients with diabetes.

https://www.bbc.co.uk/news/world-asia-india-57027829

Sumanth Gandra, Sanjay Ram, Stuart M. Levitz. The “Black Fungus” in India: The Emerging Syndemic of COVID-19–Associated Mucormycosis.Ann Intern Med. [Epub ahead of print 8 June 2021]. doi:10.7326/M21-2354

Long Covid and the risk of kinds -https://nature.us17.list-manage.com/track/click?u=2c6057c528fdc6f73fa196d9d&id=c472473a68&e=5944515236

Yes

Yes . I think so dear Dr Annwyne Houldsworth .

Hi;

A U.S. study, based on autopsies of patients who died of Covid-19, tracked the presence of the coronavirus in a large number of organs and tissues in the human body. The results show that SARS-CoV-2 can cause a disseminated infection and persist in the body for months. In particular, the virus can spread widely in the brain at an early stage. The researchers report having detected subgeneric RNAs (sgRNAs), indicators of viral replication, in all the tissues analyzed, particularly among patients who died early.

My Regards

OMICRON emerging data states it remains localized to the upper respiratory tract causing milder infections. If spread in lungs is less, other organs should also be preserved, hopefully

single cell -omics approaches should be applied systematically to more further characterize and better understand the molecular underpinnings of this "latency' process given the incidence and prevalence of long covid- eg https://www.humancellatlas.org/- further this virus is unique in human history given its worldwide distribution within 3 months, its continued seeding and reseeding through international migration (air.sea, land transport) and the emerging incidence of genetic recombination through different strains ergo multiple virus can co-infect the same cell) and probably other virus/s will also do so (medRxiv preprint doi: https://doi.org/10.1101/2021.11.19.21266601; https://www.pango.network/new-recombinant-lineage-xb/ and the incidence of reverse zoonosis ( ungulates and other animals- potential ongoing emergence of of newer strains) and the continued evolution of Sars/covid as result of selection against stratified populations of immune individuals eg non vaccinated ,single dose, double dose, boostered against a genetic background of immunocompromised )

as a species we need to wakeup as the the natural history of the planet is being rebalanced in real time through the pandemic and climate change- the next round of vaccinations specifically designed against the omicron variant need to be done synchronously and include all age groups and to occur within a 8-12 week period( vaccine immunity start to wane after this period) and just hope no newer stains do not emerge in the interim given one would predict from omicron's reproductive value/transmission rate and the fact we have already seen the emergence of multiple clades/lineages and many specific entities already https://www.pango.network/this will not be the case- ergo at best this will be a generational problem

Many thanks, Doufnoune, for this information. Where is the data on SARCoV-2 disseminated infection published and are there any other references associated with this?

Some patients that are infected by SARSCoV-2 have several recurrent infections, much more that the general population. Could this be an indication that the virus is lying latent in such patients, like Herpes Zoster?

Could the virus behave differently depending on its mechanism of entry, such as, ACE receptors in the olfactory system, leading to a neural invasion versus receptors on the alveolar cells?