How is Monkeypox different than Covid-19?

Just like Covid-19, Monkeypox (MP) is caused by a virus (this time related to smallpox), but there are major differences between these 2 diseases. 1-11

First, in contrast to Covid-19 which can easily be transmitted by casual contact through air, MP is primarily transmitted by close skin-to-skin contact (or possibly through contaminated clothing/bed linens) and sexual contact,  with great majority of current cases occurring among men who have sex with men (MSM); airborne transmission does not appear to be an important source of spread. 2

Although there is an overlap, the incubation period of MP tends to be longer (3-17 days) than that of Covid-19 which can be as few as 2 days.  Common to both diseases are flu-like symptoms such as fever, chills, muscle aches and headache, but MP is characterized by a rash that may be located on or near the genitals or anus or other areas, including hands, feet, chest face or mouth. 4

The rash (Figure) can look like pimples or blisters initially and may be painful or itchy as well. MP rash can either precede or follow flu-like symptoms after 1-4 days, or be the sole manifestation of the disease. Lymph node swelling or eye involvement (advise infected patients not to touch their eyes) may occur.  Although respiratory symptoms such as sore throat, nasal congestion and cough may occur with both diseases, shortness of breath would be unusual in MP.  A person with MP is considered contagious from onset of illness until the rash scabs over completely, which usually takes 2-4 weeks. 4,5,7,8

In contrast to Covid-19, currently there are no specific proven effective therapy against MP. However, several therapeutic agents with known activity against smallpox may be considered for those particularly at high risk of complications (eg, immunosuppressed patients, those with severe disease, exfoliative skin conditions [eg, eczema, psoriasis, Darier disease] children <8 years of age, pregnant or breast feeding patients, those with complications {eg, bacterial skin infection, pneumonia, gastroenteritis) or concurrent comorbidities.  These include an antiviral drug, Tecovirimat (TPOXX, ST-246) which can be obtained under an expanded-access protocol through the CDC in the U.S. (https://www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.html. opens in new tab) — and Vaccinia Immune Globulin Intravenous (VIGIV) also through the CDC. 3,10

There are some “good news” related to MP when compared to Covid-19. First, in contrast Covid-19, hospitalization or death from MP due to the current circulating West African strain of the virus are extremely uncommon to rare.   In fact, of more than 12,000 cases of MP in 68 countries during the first few weeks of the epidemic, only 3 deaths have been reported, none in the U.S. thus far. 2

Second, in contrast to Covid-19, a person with MP is not considered infectious before onset of symptoms. So from a public health standpoint, it may be easier to control the spread of MP in the population following identification of a case. 9

Third, vaccination of contacts with one of the 2 available vaccinia/smallpox vaccines following significant exposure to MP may prevent disease altogether or render the disease milder. Vaccines should be administered within 4 days of exposure and no longer than 14 days after.  The generally preferred vaccine against MP is a modified vaccinia virus Ankara vaccine (MVA; JYNNEOS in the U.S., Imvanex in the European Union, and Imamune in Canada) which is live but non-replicative and is associated with fewer adverse events and contraindications than the alternative, ACAM2000, a live smallpox vaccine. 3

Last, in contrast to lack of pre-existing immunity to Covid-19 in virtually everyone  when the pandemic hit over 2 years ago, a large proportion of the population who received smallpox vaccine as part childhood vaccination (ending in 1972 in the U.S.) may have at least partial immunity against MP, resulting in either no or milder disease.6,11  

Bonus Pearl: Did you know that despite its name, monkeys are not a natural host of Monkeypox, with the causative virus having been isolated from a wild monkey in Africa only once? Instead, the virus first got its name after it was identified in a colony of Asian monkeys in a laboratory in Denmark in 1958. Squirrels, rats and shrew species serve as its natural host.1

Figure: Monkeypox rash (Courtesy CDC). 

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References

  1. Cohen J. Monkeypox is a new global threat. African scientists know what the world is up against. Science. June 1 2022. Monkeypox is a new global threat. African scientists know what the world is up against | Science | AAAS
  2. Osterholm MT. Gellin B. Confronting 21st-century monkeypox. Science 2022;377:349. Confronting 21st-century monkeypox | Science
  3. Medical countermeasures available for the treatment of monkeypox. Treatment Information for Healthcare Professionals | Monkeypox | Poxvirus | CDC. Accessed August 2, 2022.
  4. Key characteristics for identifying monkeypox. Clinical Recognition | Monkeypox | Poxvirus | CDC. Accessed August 6, 2022
  5. Monkeypox signs and symptoms. Signs and Symptoms | Monkeypox | Poxvirus | CDC. Accessed August 6, 2022.
  6. Karem KL, Reynold M, Hughes C, et al. Monkeypox-induced immunity and failure of childhood smallpox vaccine to provide complete protection. Clin Vaccine Immunol 2007;14:1318-27. Monkeypox-induced immunity and failure of childhood smallpox vaccination to provide complete protection – PubMed (nih.gov)
  7. Monkeypox: Key facts. Monkeypox (who.int). Accessed August 6, 2022.
  8. Clinical presentations of Covid-19. Clinical Presentation | Clinical Care Considerations | CDC. Accessed August 6, 2022.
  9. How monkeypox spreads. How it Spreads | Monkeypox | Poxvirus | CDC. Accessed August 6, 2022.
  10. Sherwat A, Brooks JT, Birnkrant D, et al. Tecovirimat and the treatment of monkeypox—past, present, and future. N Engl J Med 2020. August 3, 2022. Tecovirimat and the Treatment of Monkeypox — Past, Present, and Future Considerations | NEJM
  11. Mandavilli A. Who is protected against monkeypox. NY Times. May 26, 2022. Who Is Protected Against Monkeypox? – The New York Times (nytimes.com)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How is Monkeypox different than Covid-19?

Why do some patients with Covid-19 develop a rebound after completing a course of Paxlovid (nirmatrelvir/ritonavir) and how common is it?

Covid-19 rebound, characterized by the recurrence of Covid-19 symptom or a new positive viral test after having tested negative, is a poorly understood phenomenon that can occur after completion of therapy with Paxlovid, Molnupiravir (another antiviral Covid-19 drug) and even in patients with acute Covid-19 who never received any specific antiviral therapy. 1-6

Based on very limited number of studies, it appears that rebound is not caused by emergence of drug resistance or absence of neutralizing immunity, rather resumption of SARS-CoV-2 replication following completion of therapy, triggering a secondary immune-mediated response that’s associated with clinical symptoms.2,3

Recent studies suggest that rebound following Paxlovid treatment may not be as common as one may think.  In a cohort of 483 high-risk patients treated with Paxlovid for Covid-19, 0.8% experienced rebound of symptoms within 30 days of diagnosis, which were generally mild at a median of 9 days after treatment, all resolving without additional antiviral therapy.3  In this study, the median age was 63 years and 93% were fully vaccinated; there were no hospitalization related to rebound or deaths. In another study (pre-print) involving over 11,000 patients treated with Paxlovid, rebound symptoms occurred in 2.3% and 5.9% of patients  7 and 30 days following therapy, respectively, with similar rates reported in patients treated with Molnupiravir.4

Interestingly, a preprint article involving 568 untreated patients with mild-moderate Covid-19 found that 27% had symptom rebound after initial improvement with 12% having viral rebound based on nasal swabs with ≥0.5 log viral RNA copies/ml. 5 So antiviral therapy for Covid-19 is not a prerequisite for rebound symptoms.

Although some have suggested that insufficient drug exposure either due to individual pharmacokinetics or insufficient duration may be the cause of rebound in treated patients,2   there is currently no evidence that additional treatment for Covid-19 is needed in these patients.6

Despite reports of rebound, Paxlovid should still be considered in selected patients with mild-moderate Covid-19 at high risk of complications to minimize the risk of hospitalization and death from Covid-19. 

Bonus Pearl: Did you know that, according to CDC, Covid-19 rebound often occurs between 2-8 days following initial recovery? 1

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References

  1. Covid-19 rebound after paxlovid treatment. May 24, 2022. COVID-19 Rebound After Paxlovid Treatment (cdc.gov)
  2. Carlin AF, Clark AE, Chaillon A, et al. Virologic and immunologic characterization of Coronavirus Disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Clin Infec Dis 2022 (June 20). Virologic and Immunologic Characterization of Coronavirus Disease 2019 Recrudescence After Nirmatrelvir/Ritonavir Treatment | Clinical Infectious Diseases | Oxford Academic (oup.com)
  3. Ranaganath N, O’Horo JC, Challner DW, et al. Rebound phenomenon after nirmatrelvir/ritonavir treatment of Coronavirus Disease-2019 in high-risk persons. Clin Infect Dis 2022 (June 14). https://doi.org/10.1093/cid/ciac481 Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons | Clinical Infectious Diseases | Oxford Academic (oup.com)
  4. Wang L, Berger NA, David PB, et al. Covid-19 rebound after Paxlovid and Molnupiravir during January-June 2022. MedRxiv 2022. COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022 | medRxiv
  5. Deo R, Choudhary MC, Moser C, et al. Viral and symptom rebound in untreated Covid-19 infection. Medrxiv 2022. Viral and Symptom Rebound in Untreated COVID-19 Infection (medrxiv.org)
  6. Covid-19 rebound after Paxlovid treatment. May 24, 2022. HAN Archive – 00467 | Health Alert Network (HAN) (cdc.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

Why do some patients with Covid-19 develop a rebound after completing a course of Paxlovid (nirmatrelvir/ritonavir) and how common is it?