Virus World

Reports of myocarditis, penile necrosis, and atypical/persistent rash requiring amputation.  Be alert for potentially severe manifestations of monkeypox in patients who are immunocompromised or co-infected with HIV, the CDC told healthcare workers on Thursday. "People who are immunocompromised due to HIV or other conditions are at higher risk for severe manifestations of monkeypox than people who are immunocompetent," the agency said in a health advisory to its Health Alert Network, adding that "the HIV status of all sexually active adults and adolescents with suspected or confirmed monkeypox should be determined."  Of the patients with severe manifestations "for whom CDC has been consulted," the majority had HIV with CD4 counts below 200 cells/mL, indicating "substantial immunosuppression," the agency noted. These severe manifestations have included cases involving atypical or persistent rash requiring amputation of an extremity; secondary bacterial or fungal infections; lesions in sensitive areas resulting in severe pain or urethral or bowel strictures; and comorbidities involving organ systems, including myocarditis, transverse myelitis, bowel lesions, penile necrosis, and others. The news arrives as the U.S. records its third known monkeypox-associated death in Ohio. To date, over 25,000 monkeypox cases have been reported in the U.S., 38% of which involved patients co-infected with HIV. Researchers have highlighted monkeypox severity and outcomes in people with HIV before.

For example, a study in The Lancet about a 2017-2018 monkeypox outbreak in Nigeria reported seven deaths in a population of 122 patients, with four of the seven co-infected with HIV.  More recently, papers on the current outbreak have reported conflicting results about the association between monkeypox severity and HIV co-infection. CDC data involving more than 1,300 monkeypox patients showed a higher rate of hospitalizations for those with HIV (8% vs 3% for those without HIV), with higher rates for those whose HIV was not virally suppressed. Conversely, German researchers reported that the clinical characteristics in HIV-infected versus non-infected monkeypox patients were largely similar. The new CDC advisory recommends that monkeypox treatment include optimization of immune function for people with immunocompromising conditions, such as limiting the use of immunosuppressive medications when "not otherwise clinically indicated," and offering antiretroviral therapy for those living with HIV. 

Severe immunocompromising conditions can including those with autoimmune disease where immunodeficiency is a clinical component; leukemia or lymphoma, transplant recipients; and those treated with high-dose steroids, alkylating agents, antimetabolites, radiation, or tumor necrosis factor (TNF) inhibitors.  On a case-by-case basis, medications such as oral and intravenous tecovirimat (Tpoxx), cidofovir or brincidofovir, and vaccinia immune globulin intravenous should be considered, "although there are no data on effectiveness in treating human monkeypox with these medical countermeasures," according to the CDC. Clinicians should gather repeat lesion swabs in patients with persistent monkeypox DNA, and continue tecovirimat beyond 14 days (but not more than 90 days), "until there is clinical improvement," the advisory stated. Modifications to the dose, frequency, and duration of tecovirimat may be necessary, depending on the patient's clinical condition, disease progression, or therapeutic response. The advisory encouraged clinicians to consult with the CDC Monkeypox Response Clinical Escalations team when appropriate.  The following severe manifestations seen in monkeypox patients were reported to the CDC, although the advisory did not include information about HIV status:

• Atypical or persistent rash with coalescing or necrotic lesions, or both, some of which have required extensive surgical debridement or amputation of an affected extremity

• Lesions on a significant proportion of the total body surface area, which may be associated with edema and secondary bacterial or fungal infections among other complications

• Lesions in sensitive areas (including mucosal surfaces such as the oropharynx, urethra, rectum, and vagina) resulting in severe pain that interferes with activities of daily living

• Bowel lesions that are exudative or cause significant tissue edema, leading to obstruction

• Severe lymphadenopathy that can be necrotizing or obstructing (such as in airways)

• Lesions leading to stricture and scar formation resulting in significant morbidity such as urethral and bowel strictures, phimosis, and facial scarring

The CDC advisory also noted reports of individuals with severe monkeypox involving multiple organ systems and associated comorbidities, including oropharyngeal lesions inhibiting oral intake; pulmonary involvement with nodular lesions; neurologic conditions, including encephalitis and transverse myelitis; cardiac complications, including myocarditis and pericardial disease; ocular conditions including severe conjunctivitis; sight-threatening corneal ulcerations; and urologic involvement including urethritis and penile necrosis. The advisory also urged healthcare providers and public health jurisdictions to encourage patients to enroll in the AIDS Clinical Trials Group STOMP trial to evaluate the efficacy of tecovirimat for monkeypox.

CDC Health Advisory published September 29, 2022:

https://emergency.cdc.gov/han/2022/han00475.asp 

The "mRNA COVID-19 vaccines may be administered to people with underlying medical conditions provided they have not had a severe allergic reaction to any of the ingredients in the vaccine," the CDC wrote in updated guidance. The Centers for Disease Control and Prevention (CDC) issued new COVID-19 vaccine guidance, which indicates that those with preexisting medical conditions should receive the vaccine. "Adults of any age with certain underlying medical conditions are at increased risk for severe illness from the virus that causes COVID-19," the CDC wrote in updated guidance on December 26, adding that "mRNA COVID-19 vaccines may be administered to people with underlying medical conditions provided they have not had a severe allergic reaction to any of the ingredients in the vaccine." The two different vaccines that are currently being administered to Americans use mRNA technology, which tells the body to create antibodies to combat the virus, instead of using a weakened version of the virus. The two vaccines include one developed by Pfizer and German biotech company, BioNTech and the other developed by Moderna.  The CDC's COVID-19 vaccine update provides guidance for those with several different preexisting medical conditions including weakened immune systems, autoimmune conditions, Guillain-Barre syndrome and Bell's palsy.

As the CDC notes, people with HIV and weakened immune systems "due to other illnesses or medication might be at increased risk for severe COVID-19." The CDC states that these people should receive a COVID-19 vaccine but notes that "information about the safety of mRNA COVID-19 vaccines" for this group is not yet available. "People living with HIV were included in clinical trials, though safety data specific to this group are not yet available at this time," the CDC said.  The CDC provides similar guidance for those with autoimmune conditions, stating that this group should receive a COVID-19 vaccine but adds that "they should be aware that no data are currently available on the safety of mRNA COVID-19 vaccines for them." According to the CDC, to date, there have been no reported cases of Guillain-Barre syndrome after a person received a COVID-19 vaccine during clinical trials and people who previously had GBS should receive the vaccine. On December 17, the Food and Drug Administration reported cases of Bell's palsy in people who received the Pfizer and Moderna vaccines during clinical trials. Bell's palsy is a temporary facial paralysis, but in the CDC's updated guidance, it states that the FDA "does not consider these [cases] to be above the rate expected in the general population." "They have not concluded these cases were caused by vaccination. Therefore, persons who have previously had Bell's palsy may receive an mRNA COVID-19 vaccine," the CDC stated.

The CDC's updated guidance also states that even after receiving a COVID-19 vaccine, people should continue to follow the current guidance to combat the virus. The current guidelines include wearing a protective face mask while in public, following social distancing measures, washing hands, and following quarantine guidance after being exposed to the virus.  The updated guidance comes as the CDC and many other health authorities have said that those with preexisting medical conditions are at a heightened risk of developing serious cases of the novel virus. Newsweek reached out to the CDC for comment but did not receive a response in time for publication. The updated guidance comes as the CDC and many other health authorities have said that those with preexisting medical conditions are at a heightened risk of developing serious cases of the novel virus. Newsweek reached out to the CDC for comment but did not receive a response in time for publication.

Updated CDC guidelines (Dec. 29, 2020):

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/underlying-conditions.html

Cele et al. examine a SARS-CoV-2 infection persisting over 6 months, starting as ancestral virus but evolving various mutations found in Omicron and other variants. The evolved virus substantially but incompletely escaped BNT162b2-elicited immunity as well as neutralization by self-plasma and showed extensive escape from neutralization elicited by Delta infections.

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa, infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral but evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections.

Published in Cell and Host Microbe (Jan. 13, 2022):

https://doi.org/10.1016/j.chom.2022.01.005