Introduction
Literature Search Strategy
Impact of COVID-19 Pandemic on International Travel
Relevant Effects of COVID-19 Pandemic and Mitigation Strategies
Travel-Related Transmission of COVID-19
Arrival date/incident date | Origin of cruise/flight/other transport/participants | Incident location | Number of cases | Comments | References |
---|---|---|---|---|---|
Cruise ships | |||||
January–February 2020 | Japan | Hong Kong, Japan | Diamond Princess: 712 cases (554 of 2666 guests, 152 of 1045 crew), 9 deaths | Of 437 Americans and their travel companions on the ship, 114 (26%) were SARS-CoV-2-positive. Attack rate was 18% in those without infected cabinmates vs. 63% with asymptomatic infected cabinmate vs. 81% with symptomatic infected cabinmate. Estimated infection rate was 79% if no intervention had been implemented | |
February–March 2020 | USA | USA | Grand Princess 2 voyages: 123 cases (among 2422 guests and 1111 crew) and 5 deaths | Only 30% of guests and crew were tested. Of 469 persons with available test results, 78 (16.6%) were SARS-CoV-2-positive | [43] |
March 2020 | Australia | Australia | Ruby Princess: 907 primary cases (605 of 2647 guests and 202 of 1151 crew), 29 deaths | 120 people on board the Ruby Princess met the case definition for COVID-19 at the time of disembarkment; in April 2020, the outbreak was linked to 13% of all COVID-19 cases in Australia | [37] |
July–August 2020 | Norway | Norway | MS Roald Amundsen: 42 cases among 167 crewmembers and 28 cases among 391 passengers (attack rates 25.2% and 7.2%, respectively) | Outbreaks of lineage B.1.36 occurred on 2 1-week voyages, from Tromsø around the Svalbard archipelago | [46] |
Air travel and quarantine isolation facilities | |||||
March 2020 | UK | Vietnam | 1 index case, followed by 16 cases among 201 passengers and 16 crew | Flight VN54: Among 16 cases, 12 (75%) were passengers in business class along with the only symptomatic case (attack rate 62%). Seating proximity had increased infection risk (risk ratio 7.3) | [47] |
March 2020 | USA | Hong Kong | 4 cases (2 passengers among 294 passengers, and 2 crew) | The near full-length viral genomes from the 4 cases were 100% identical, were phylogenetically grouped to clade G, and were distinct from 189 other Hong Kong viral sequences collected during January–May | [48] |
March 2020 | Australia | Australia | 29 cases PCR-confirmed (among 241 passengers on board) | 6 initial cases identified to be on flight led to PCR confirmation of 18 primary cases: most had disembarked from cruise ships (Ovation of the Seas; Ruby Princess) before the Sydney-Perth flight, and one passenger had travelled from the USA, and 11 secondary cases. All WGS available were A2-RP strain | [39] |
September 2020 | India | New Zealand | Index cases tested positive in MIQ @3 days after flight, followed by sequential identification of 7 additional cases in MIQ and in the community | A chain of transmission without direct person-to-person contact by aerosol within MIQ; transmission in-flight, and within households; WGS analysis helped to identify probable direction of transmission between cases | [49] |
September–October 2020 | UAE | New Zealand | 7 positive PCRs among 86 passengers on a flight from Dubai, UAE | Flight EK448: cases originated from Switzerland (2), Ukraine, Ireland, India, South Africa (2) before layover in Dubai; 5 had negative pre-departure PCR. All 7 SARS-CoV-2 genomes were genetically identical, except for a single mutation in 1 sample | [50•] |
December 2020 | International | Ireland | 165 cases on 134 flights; 40% symptomatic on board | National study of SARS-CoV-2 on 2098 inbound international flights and estimated 135,900 passengers in December 2020; secondary attack rate of 7.0%, higher on flights ≥ 5 h | [51] |
April 2021 | India | Hong Kong | 59 PCR-confirmed cases among 146 passengers; 20% symptomatic | Delhi-Hong Kong flight: 5 positive upon arrival. 7 were estimated to be infected prior to travel, 41 infected during transit, 11 infected in quarantine. WGS detected 3 variants Kappa, Alpha, and Delta | [52] |
April 2021 | India | Australia | 47 cases aboard 2 flights carrying 345 passengers; 14% of arrival cases symptomatic | Based on analysis of SARS-CoV-2 genomic clusters, transmission occurred despite mandatory mask wearing and pre-departure testing. Pre-departure quarantine and enhanced pre-departure testing were implemented for subsequent flights | [53•] |
April–June 2021 | International | Spain | 196 PCR-confirmed among 45,211 travelers initially tested by rapid antigen on arrival to Madrid international airport | Most cases came from Colombia (114), followed by the Dominican Republic (30) and Peru (12). WGS identified B.1.621 (Mu) to be the most frequently occurring variant, but others were also found, including Alpha, Beta, Gamma, and Delta. This showed potentially infectious passengers on board but did not trace their contacts to identify in-flight transmission | [54] |
July 2021 | Philippines, United Arab Emirates | New Zealand | Traveler A arrived from the Philippines and traveler E from a 5-person travel group (BCDEF) from UAE tested positive. Travelers B, C, and D subsequently tested positive; viral sequences matched A | In the MIF, traveler A and group BCDEF occupied rooms > 2 m apart across a hall and never had direct contact | [55] |
Other transport or group travel | |||||
January 2020 | China | China (Beijing ex Wuhan) | A family of 3 travelled by train from Beijing to Wuhan to visit the younger son. One parent developed respiratory symptoms and COVID-19 was confirmed; subsequently, the other family members were confirmed | The younger son had been living in Wuhan since August 2019. The father travelled to Wuhan on January 4, 2020, and the mother and the elder son went to Wuhan on January 18, 2020. On January 20, they took the 4-h train to return to Beijing without wearing masks. Once they arrived in Beijing, they drove their own car back home and were isolated at home. The mother developed respiratory symptoms on January 23 | [56] |
August 2021 | Israel | Iceland | Among 25 travelers on a 12-day tour (96% were fully vaccinated with 2 doses of BNT162b2), 21 became PCR-positive pre-departure for Israel or upon landing; attack rate 84% | All 25 travelers were PCR negative pre-travel, 15 (60%) tested PCR-positive pre-departure from Reykjavik, and 6 more tested positive upon landing. All cases were mild and none was hospitalized. The tour had a local bus driver (vaccinated), dedicated bus, with little indoor contacts with locals or other travelers | [57] |
October 2021 | Japan | Japan | 19 cases identified (18 participants and 1 bus staff), the index case and majority of cases were on bus 1 (18/19 [95%], attack rate 44%), and one participant case on bus 4 (1/19 [5%], AR 3%) | 158 persons (146 participants and 12 staff) participated in a 4-day tour on four buses visited 11 tourist sites around Hokkaido, Japan, in October 2020: 41 for bus 1, 39 for bus 2, 40 for bus 3, and 38 for bus 4 | [58] |
May 2021 | International | Nepal | 14 COVID-19-positive Everest travellers presented to CIWEC in 2021 | 5 had 2-dose vaccination with ChAdOx1 nCoV-19 (n = 2), Sinopharm (n = 1), Sputnik V (n = 1), and mRNA-1273 (n = 1), and one had single dose of ChAdOx1 nCoV-19. Among these, 3 required hospital admission and 3 were treated as outpatients. No death was reported | [59] |
Mass gatherings and superspreading events | |||||
February–March 2020 | France | Switzerland | Phylogenetic analysis of positive SARS-CoV-2 tests determined the origin of B.1-C15324T to mid-February in the trinational region around Basel. Genome analysis of multiple early cases identified attendance at a religious mass gathering event in Alsace, France | The outbreak in Basel was dominated by lineage B.1 (83.6%), detected in early March. Within B.1, the majority of samples fall within a clade including 157 identical sequences at the root of the “Basel cluster,” some of which were traced to regional spreading events. A mass gathering event was the predominant initial source of cases | [60] |
February–March 2020 | USA | USA | An international business conference with one COVID-19-infected international attendee led to domestic and international spread, and sustained community transmission, including outbreaks in homeless and other higher-risk communities, resulting in > 300,000 cases | Genomic analysis of 772 SARS-CoV-2 sample identified > 120 introductions of SARS-CoV-2 into the Boston area, but only a few led to most local transmission: 29% of the introductions were responsible for 85% of the cases, including the international business conference. Most of the introductions occurred in March and early April, primarily from elsewhere in North America and from Europe | [61] |
March 2020 | Jordan | Jordan | An index patient at a wedding was linked to 85 cases that were confirmed in the 4 weeks following the event | About 360 persons attended a 2-h wedding ceremony and party at an indoor venue and were exposed to the index patient, the bride’s father. The wedding was linked to 85 subsequent positives where 76 (89.4%) attended the wedding, and 9 (10.6%) were close contacts of confirmed cases from the wedding | [62] |
January–April 2021 | India | India | Daily COVID-19 cases increased from 37 to 144 (276%) in Haridwar. In Uttarakhand state, daily cases increased from 138 to 480 (236%) and in India, from 45,600 to 92,754 (92%) during this MG | Kumbh Mela mass gathering (MG) took place from 14 January 2021 to 29 April 2021 at Haridwar, the capital city of the state of Uttarakhand, India. The estimated attendance was ~ 10–20 million people between 1 April 2021 and 30 April 2021 | [63] |
June–July 2021 | International | Netherlands, Denmark, Scotland, England, Germany, Italy, Russia, Spain | An increase in COVID-19 incidence per 100,000 population from the start of Euro2020 was observed across 7 of 11 host cities/regions: Netherlands (1629%), Denmark (210%), Scotland (57%), England (382%), Germany (9%), Italy (104%), Russia (196%) and Spain (135%) | COVID-19 cases across declined in May 2021 in Europe as vaccination rates were on the rise. As Euro2020 initiated in June 2021, an increase in COVID-19 cases was observed along with Delta variant, across all countries in Europe. Except for Budapest which had no increase, all host cities/regions exhibited an increase between the start of the matches and 15 days after the last match played in the city/region. Munich-Germany experienced a minimal increase | [64] |
November 2021 | USA | USA | Overall 119 (2.6%) persons from 16 jurisdictions were positive from among 4560 SARS-CoV-2 tests | An indoor convention in New York City was attended by about 53,000 vaccinated persons from 52 US jurisdictions and 30 foreign countries. Compared with test-negative respondents, test-positive respondents were more likely to report attending bars, karaoke, or nightclubs, and eating or drinking indoors near others for at least 15 min. Genomic sequencing of 20 specimens identified the SARS-CoV-2 B.1.617.2 (Delta) variant (AY.25 and AY.103 sublineages) in 15 (75%) cases, and Omicron variant (BA.1 sublineage) in five (25%) cases |
COVID-19 Mitigation and Control Measures
Pre-travel Testing and Airport Screening Protocols
Protective Efficacy of Masks and Social Distancing During Air Travel
Protective Measures to Mitigate SARS-CoV-2 Spread on Cruise Ships
Game-Changing Therapeutic Advances
Therapeutic agent | Status | Current indication (FDA EUA, NIH) | Possible application for travel | Comments | References |
---|---|---|---|---|---|
Tixagevimab-cilgavimab (Evusheld) | FDA, EUA | Pre-exposure prophylaxis (PrEP) for adults and adolescents (aged ≥ 12 years and weighing ≥ 40 kg) who do not have SARS-CoV-2 infection, who have not been recently exposed to an individual with SARS-CoV-2 infection, AND who have: •Moderate to severe immunocompromise and may have an inadequate immune response to COVID-19 vaccination; or •A contraindication hence unable to be fully vaccinated with COVID-19 vaccines | Pre-exposure prophylaxis for travelers at high risk of severe disease from COVID-19, who have no symptoms of COVID-19 and no confirmed exposure to COVID-19 within prior 5 days | Long-acting human monoclonal antibody that binds to the spike protein receptor-binding domain (RBD) of SARS-CoV-2 preventing binding affinity to ACE2 | [100] |
PROVENT, the unpublished randomized, double-blind, placebo-controlled trial of adults > 59 years or with a pre-specified chronic medical condition or at increased risk of SARS-CoV-2 infection who had not received a COVID-19 vaccine and no history of SARS-CoV-2 infection, found a 77% reduced risk of COVID-19 compared to placebo | [96••] | ||||
Nirmatrelvir-ritonavir (Paxlovid) | FDA, EUA | Outpatient treatment of mild-moderate COVID-19 infection in patients at high risk for progressing to severe infection and possible hospitalization | Self-treatment for COVID-19: start within 5 days of symptom onset or positive viral test | A viral protease that cleaves 2 viral polyproteins leading to antiviral activity against all human coronaviruses, and packaged with ritonavir, a cytochrome P450 (CYP) 3A4 inhibitor, to boost nirmatrelvir concentrations | [98] |
EPIC-HR trial demonstrated that starting nirmatrelvir-ritonavir in adults with mild to moderate COVID-19 within 5 days of symptom onset reduced the risk of hospitalization or death through day 28 by 89% compared to placebo | |||||
Molnupiravir | FDA, EUA | Outpatient treatment of mild-moderate COVID-19 infection in patients at high risk for progressing to severe infection and possible hospitalization (only in the case that alternative treatment options are not available or appropriate) | Self-treatment for COVID-19: start within 5 days of symptom onset or positive viral test | An oral prodrug of beta-D-N4-hydroxycytidine (NHC), a ribonucleoside that has broad antiviral activity against RNA viruses and inhibits RNA polymerase | [99] |
In the MOVe-OUT trial, molnupiravir reduced the rate of hospitalization or death by 30% compared to placebo |